Pleiotrophin regulates microglia-mediated neuroinflammation

Background Pleiotrophin (PTN) is a cytokine found highly upregulated in the brain in different disorders characterized by overt neuroinflammation such as neurodegenerative diseases, drug addiction, traumatic injury, and ischemia. In the present work, we have explored whether PTN modulates neuroinflammation and if Toll-like receptor 4 (TLR4), crucial in the initiation of an immune response, is involved. Methods In immunohistochemistry assays, we studied lipopolysaccharide (LPS, 7.5 mg/kg i.p.)-induced changes in glial fibrillary acidic protein (GFAP, astrocyte marker) and ionized calcium-binding adaptor molecule 1 (Iba1, microglia marker) expression in the prefrontal cortex (PFC) and striatum of mice with transgenic PTN overexpression in the brain (PTN-Tg) and in wild-type (WT) mice. Cytokine protein levels were assessed in the PFC by X-MAP technology. The influence of TLR4 signaling in LPS effects in both genotypes was assessed by pretreatment with the TLR4 antagonist (TAK-242, 3.0 mg/kg i.p.). Murine BV2 microglial cells were treated with PTN (0.5 μg/ml) and LPS (1.0 μg/ml) and assessed for the release of nitric oxide (NO). Results We found that LPS-induced microglial activation is significantly increased in the PFC of PTN-Tg mice compared to that of WT mice. The levels of TNF-α, IL-6, and MCP-1 in response to LPS were significantly increased in the PFC of PTN-Tg mice compared to that of WT mice. Pretreatment with TAK-242 efficiently blocked increases in cytokine contents in a similar manner in both genotypes. Concomitant incubation of BV2 cells with LPS and PTN significantly potentiated the production of NO compared to cells only treated with LPS. Conclusions Our findings identify for the first time that PTN is a novel and potent regulator of neuroinflammation. Pleiotrophin potentiates LPS-stimulated microglia activation. Our results suggest that regulation of the PTN signaling pathways may constitute new therapeutic opportunities particularly in those neurological disorders characterized by increased PTN cerebral levels and neuroinflammation. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Fernández-Calle, Rosalía [verfasserIn] Vicente-Rodríguez, Marta Gramage, Esther Pita, Jimena Pérez-García, Carmen Ferrer-Alcón, Marcel Uribarri, María Ramos, María P. Herradón, Gonzalo

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2017

Schlagwörter:	Microgliosis Microglia activation Midkine Neuroimmune response Neuroinflammation Pleiotrophin TLR4

Anmerkung:	© The Author(s). 2017

Übergeordnetes Werk:	Enthalten in: Journal of neuroinflammation - London : BioMed Central, 2004, 14(2017), 1 vom: 04. März
Übergeordnetes Werk:	volume:14 ; year:2017 ; number:1 ; day:04 ; month:03

Links:	Volltext

DOI / URN:	10.1186/s12974-017-0823-8

Katalog-ID:	SPR029107229

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520			\|a Background Pleiotrophin (PTN) is a cytokine found highly upregulated in the brain in different disorders characterized by overt neuroinflammation such as neurodegenerative diseases, drug addiction, traumatic injury, and ischemia. In the present work, we have explored whether PTN modulates neuroinflammation and if Toll-like receptor 4 (TLR4), crucial in the initiation of an immune response, is involved. Methods In immunohistochemistry assays, we studied lipopolysaccharide (LPS, 7.5 mg/kg i.p.)-induced changes in glial fibrillary acidic protein (GFAP, astrocyte marker) and ionized calcium-binding adaptor molecule 1 (Iba1, microglia marker) expression in the prefrontal cortex (PFC) and striatum of mice with transgenic PTN overexpression in the brain (PTN-Tg) and in wild-type (WT) mice. Cytokine protein levels were assessed in the PFC by X-MAP technology. The influence of TLR4 signaling in LPS effects in both genotypes was assessed by pretreatment with the TLR4 antagonist (TAK-242, 3.0 mg/kg i.p.). Murine BV2 microglial cells were treated with PTN (0.5 μg/ml) and LPS (1.0 μg/ml) and assessed for the release of nitric oxide (NO). Results We found that LPS-induced microglial activation is significantly increased in the PFC of PTN-Tg mice compared to that of WT mice. The levels of TNF-α, IL-6, and MCP-1 in response to LPS were significantly increased in the PFC of PTN-Tg mice compared to that of WT mice. Pretreatment with TAK-242 efficiently blocked increases in cytokine contents in a similar manner in both genotypes. Concomitant incubation of BV2 cells with LPS and PTN significantly potentiated the production of NO compared to cells only treated with LPS. Conclusions Our findings identify for the first time that PTN is a novel and potent regulator of neuroinflammation. Pleiotrophin potentiates LPS-stimulated microglia activation. Our results suggest that regulation of the PTN signaling pathways may constitute new therapeutic opportunities particularly in those neurological disorders characterized by increased PTN cerebral levels and neuroinflammation.
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allfields	10.1186/s12974-017-0823-8 doi (DE-627)SPR029107229 (SPR)s12974-017-0823-8-e DE-627 ger DE-627 rakwb eng Fernández-Calle, Rosalía verfasserin aut Pleiotrophin regulates microglia-mediated neuroinflammation 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Pleiotrophin (PTN) is a cytokine found highly upregulated in the brain in different disorders characterized by overt neuroinflammation such as neurodegenerative diseases, drug addiction, traumatic injury, and ischemia. In the present work, we have explored whether PTN modulates neuroinflammation and if Toll-like receptor 4 (TLR4), crucial in the initiation of an immune response, is involved. Methods In immunohistochemistry assays, we studied lipopolysaccharide (LPS, 7.5 mg/kg i.p.)-induced changes in glial fibrillary acidic protein (GFAP, astrocyte marker) and ionized calcium-binding adaptor molecule 1 (Iba1, microglia marker) expression in the prefrontal cortex (PFC) and striatum of mice with transgenic PTN overexpression in the brain (PTN-Tg) and in wild-type (WT) mice. Cytokine protein levels were assessed in the PFC by X-MAP technology. The influence of TLR4 signaling in LPS effects in both genotypes was assessed by pretreatment with the TLR4 antagonist (TAK-242, 3.0 mg/kg i.p.). Murine BV2 microglial cells were treated with PTN (0.5 μg/ml) and LPS (1.0 μg/ml) and assessed for the release of nitric oxide (NO). Results We found that LPS-induced microglial activation is significantly increased in the PFC of PTN-Tg mice compared to that of WT mice. The levels of TNF-α, IL-6, and MCP-1 in response to LPS were significantly increased in the PFC of PTN-Tg mice compared to that of WT mice. Pretreatment with TAK-242 efficiently blocked increases in cytokine contents in a similar manner in both genotypes. Concomitant incubation of BV2 cells with LPS and PTN significantly potentiated the production of NO compared to cells only treated with LPS. Conclusions Our findings identify for the first time that PTN is a novel and potent regulator of neuroinflammation. Pleiotrophin potentiates LPS-stimulated microglia activation. Our results suggest that regulation of the PTN signaling pathways may constitute new therapeutic opportunities particularly in those neurological disorders characterized by increased PTN cerebral levels and neuroinflammation. Microgliosis (dpeaa)DE-He213 Microglia activation (dpeaa)DE-He213 Midkine (dpeaa)DE-He213 Neuroimmune response (dpeaa)DE-He213 Neuroinflammation (dpeaa)DE-He213 Pleiotrophin (dpeaa)DE-He213 TLR4 (dpeaa)DE-He213 Vicente-Rodríguez, Marta aut Gramage, Esther aut Pita, Jimena aut Pérez-García, Carmen aut Ferrer-Alcón, Marcel aut Uribarri, María aut Ramos, María P. aut Herradón, Gonzalo aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 14(2017), 1 vom: 04. März (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:14 year:2017 number:1 day:04 month:03 https://dx.doi.org/10.1186/s12974-017-0823-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2017 1 04 03
spelling	10.1186/s12974-017-0823-8 doi (DE-627)SPR029107229 (SPR)s12974-017-0823-8-e DE-627 ger DE-627 rakwb eng Fernández-Calle, Rosalía verfasserin aut Pleiotrophin regulates microglia-mediated neuroinflammation 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Pleiotrophin (PTN) is a cytokine found highly upregulated in the brain in different disorders characterized by overt neuroinflammation such as neurodegenerative diseases, drug addiction, traumatic injury, and ischemia. In the present work, we have explored whether PTN modulates neuroinflammation and if Toll-like receptor 4 (TLR4), crucial in the initiation of an immune response, is involved. Methods In immunohistochemistry assays, we studied lipopolysaccharide (LPS, 7.5 mg/kg i.p.)-induced changes in glial fibrillary acidic protein (GFAP, astrocyte marker) and ionized calcium-binding adaptor molecule 1 (Iba1, microglia marker) expression in the prefrontal cortex (PFC) and striatum of mice with transgenic PTN overexpression in the brain (PTN-Tg) and in wild-type (WT) mice. Cytokine protein levels were assessed in the PFC by X-MAP technology. The influence of TLR4 signaling in LPS effects in both genotypes was assessed by pretreatment with the TLR4 antagonist (TAK-242, 3.0 mg/kg i.p.). Murine BV2 microglial cells were treated with PTN (0.5 μg/ml) and LPS (1.0 μg/ml) and assessed for the release of nitric oxide (NO). Results We found that LPS-induced microglial activation is significantly increased in the PFC of PTN-Tg mice compared to that of WT mice. The levels of TNF-α, IL-6, and MCP-1 in response to LPS were significantly increased in the PFC of PTN-Tg mice compared to that of WT mice. Pretreatment with TAK-242 efficiently blocked increases in cytokine contents in a similar manner in both genotypes. Concomitant incubation of BV2 cells with LPS and PTN significantly potentiated the production of NO compared to cells only treated with LPS. Conclusions Our findings identify for the first time that PTN is a novel and potent regulator of neuroinflammation. Pleiotrophin potentiates LPS-stimulated microglia activation. Our results suggest that regulation of the PTN signaling pathways may constitute new therapeutic opportunities particularly in those neurological disorders characterized by increased PTN cerebral levels and neuroinflammation. Microgliosis (dpeaa)DE-He213 Microglia activation (dpeaa)DE-He213 Midkine (dpeaa)DE-He213 Neuroimmune response (dpeaa)DE-He213 Neuroinflammation (dpeaa)DE-He213 Pleiotrophin (dpeaa)DE-He213 TLR4 (dpeaa)DE-He213 Vicente-Rodríguez, Marta aut Gramage, Esther aut Pita, Jimena aut Pérez-García, Carmen aut Ferrer-Alcón, Marcel aut Uribarri, María aut Ramos, María P. aut Herradón, Gonzalo aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 14(2017), 1 vom: 04. März (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:14 year:2017 number:1 day:04 month:03 https://dx.doi.org/10.1186/s12974-017-0823-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2017 1 04 03
allfields_unstemmed	10.1186/s12974-017-0823-8 doi (DE-627)SPR029107229 (SPR)s12974-017-0823-8-e DE-627 ger DE-627 rakwb eng Fernández-Calle, Rosalía verfasserin aut Pleiotrophin regulates microglia-mediated neuroinflammation 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Pleiotrophin (PTN) is a cytokine found highly upregulated in the brain in different disorders characterized by overt neuroinflammation such as neurodegenerative diseases, drug addiction, traumatic injury, and ischemia. In the present work, we have explored whether PTN modulates neuroinflammation and if Toll-like receptor 4 (TLR4), crucial in the initiation of an immune response, is involved. Methods In immunohistochemistry assays, we studied lipopolysaccharide (LPS, 7.5 mg/kg i.p.)-induced changes in glial fibrillary acidic protein (GFAP, astrocyte marker) and ionized calcium-binding adaptor molecule 1 (Iba1, microglia marker) expression in the prefrontal cortex (PFC) and striatum of mice with transgenic PTN overexpression in the brain (PTN-Tg) and in wild-type (WT) mice. Cytokine protein levels were assessed in the PFC by X-MAP technology. The influence of TLR4 signaling in LPS effects in both genotypes was assessed by pretreatment with the TLR4 antagonist (TAK-242, 3.0 mg/kg i.p.). Murine BV2 microglial cells were treated with PTN (0.5 μg/ml) and LPS (1.0 μg/ml) and assessed for the release of nitric oxide (NO). Results We found that LPS-induced microglial activation is significantly increased in the PFC of PTN-Tg mice compared to that of WT mice. The levels of TNF-α, IL-6, and MCP-1 in response to LPS were significantly increased in the PFC of PTN-Tg mice compared to that of WT mice. Pretreatment with TAK-242 efficiently blocked increases in cytokine contents in a similar manner in both genotypes. Concomitant incubation of BV2 cells with LPS and PTN significantly potentiated the production of NO compared to cells only treated with LPS. Conclusions Our findings identify for the first time that PTN is a novel and potent regulator of neuroinflammation. Pleiotrophin potentiates LPS-stimulated microglia activation. Our results suggest that regulation of the PTN signaling pathways may constitute new therapeutic opportunities particularly in those neurological disorders characterized by increased PTN cerebral levels and neuroinflammation. Microgliosis (dpeaa)DE-He213 Microglia activation (dpeaa)DE-He213 Midkine (dpeaa)DE-He213 Neuroimmune response (dpeaa)DE-He213 Neuroinflammation (dpeaa)DE-He213 Pleiotrophin (dpeaa)DE-He213 TLR4 (dpeaa)DE-He213 Vicente-Rodríguez, Marta aut Gramage, Esther aut Pita, Jimena aut Pérez-García, Carmen aut Ferrer-Alcón, Marcel aut Uribarri, María aut Ramos, María P. aut Herradón, Gonzalo aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 14(2017), 1 vom: 04. März (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:14 year:2017 number:1 day:04 month:03 https://dx.doi.org/10.1186/s12974-017-0823-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2017 1 04 03
allfieldsGer	10.1186/s12974-017-0823-8 doi (DE-627)SPR029107229 (SPR)s12974-017-0823-8-e DE-627 ger DE-627 rakwb eng Fernández-Calle, Rosalía verfasserin aut Pleiotrophin regulates microglia-mediated neuroinflammation 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Pleiotrophin (PTN) is a cytokine found highly upregulated in the brain in different disorders characterized by overt neuroinflammation such as neurodegenerative diseases, drug addiction, traumatic injury, and ischemia. In the present work, we have explored whether PTN modulates neuroinflammation and if Toll-like receptor 4 (TLR4), crucial in the initiation of an immune response, is involved. Methods In immunohistochemistry assays, we studied lipopolysaccharide (LPS, 7.5 mg/kg i.p.)-induced changes in glial fibrillary acidic protein (GFAP, astrocyte marker) and ionized calcium-binding adaptor molecule 1 (Iba1, microglia marker) expression in the prefrontal cortex (PFC) and striatum of mice with transgenic PTN overexpression in the brain (PTN-Tg) and in wild-type (WT) mice. Cytokine protein levels were assessed in the PFC by X-MAP technology. The influence of TLR4 signaling in LPS effects in both genotypes was assessed by pretreatment with the TLR4 antagonist (TAK-242, 3.0 mg/kg i.p.). Murine BV2 microglial cells were treated with PTN (0.5 μg/ml) and LPS (1.0 μg/ml) and assessed for the release of nitric oxide (NO). Results We found that LPS-induced microglial activation is significantly increased in the PFC of PTN-Tg mice compared to that of WT mice. The levels of TNF-α, IL-6, and MCP-1 in response to LPS were significantly increased in the PFC of PTN-Tg mice compared to that of WT mice. Pretreatment with TAK-242 efficiently blocked increases in cytokine contents in a similar manner in both genotypes. Concomitant incubation of BV2 cells with LPS and PTN significantly potentiated the production of NO compared to cells only treated with LPS. Conclusions Our findings identify for the first time that PTN is a novel and potent regulator of neuroinflammation. Pleiotrophin potentiates LPS-stimulated microglia activation. Our results suggest that regulation of the PTN signaling pathways may constitute new therapeutic opportunities particularly in those neurological disorders characterized by increased PTN cerebral levels and neuroinflammation. Microgliosis (dpeaa)DE-He213 Microglia activation (dpeaa)DE-He213 Midkine (dpeaa)DE-He213 Neuroimmune response (dpeaa)DE-He213 Neuroinflammation (dpeaa)DE-He213 Pleiotrophin (dpeaa)DE-He213 TLR4 (dpeaa)DE-He213 Vicente-Rodríguez, Marta aut Gramage, Esther aut Pita, Jimena aut Pérez-García, Carmen aut Ferrer-Alcón, Marcel aut Uribarri, María aut Ramos, María P. aut Herradón, Gonzalo aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 14(2017), 1 vom: 04. März (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:14 year:2017 number:1 day:04 month:03 https://dx.doi.org/10.1186/s12974-017-0823-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2017 1 04 03
allfieldsSound	10.1186/s12974-017-0823-8 doi (DE-627)SPR029107229 (SPR)s12974-017-0823-8-e DE-627 ger DE-627 rakwb eng Fernández-Calle, Rosalía verfasserin aut Pleiotrophin regulates microglia-mediated neuroinflammation 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Pleiotrophin (PTN) is a cytokine found highly upregulated in the brain in different disorders characterized by overt neuroinflammation such as neurodegenerative diseases, drug addiction, traumatic injury, and ischemia. In the present work, we have explored whether PTN modulates neuroinflammation and if Toll-like receptor 4 (TLR4), crucial in the initiation of an immune response, is involved. Methods In immunohistochemistry assays, we studied lipopolysaccharide (LPS, 7.5 mg/kg i.p.)-induced changes in glial fibrillary acidic protein (GFAP, astrocyte marker) and ionized calcium-binding adaptor molecule 1 (Iba1, microglia marker) expression in the prefrontal cortex (PFC) and striatum of mice with transgenic PTN overexpression in the brain (PTN-Tg) and in wild-type (WT) mice. Cytokine protein levels were assessed in the PFC by X-MAP technology. The influence of TLR4 signaling in LPS effects in both genotypes was assessed by pretreatment with the TLR4 antagonist (TAK-242, 3.0 mg/kg i.p.). Murine BV2 microglial cells were treated with PTN (0.5 μg/ml) and LPS (1.0 μg/ml) and assessed for the release of nitric oxide (NO). Results We found that LPS-induced microglial activation is significantly increased in the PFC of PTN-Tg mice compared to that of WT mice. The levels of TNF-α, IL-6, and MCP-1 in response to LPS were significantly increased in the PFC of PTN-Tg mice compared to that of WT mice. Pretreatment with TAK-242 efficiently blocked increases in cytokine contents in a similar manner in both genotypes. Concomitant incubation of BV2 cells with LPS and PTN significantly potentiated the production of NO compared to cells only treated with LPS. Conclusions Our findings identify for the first time that PTN is a novel and potent regulator of neuroinflammation. Pleiotrophin potentiates LPS-stimulated microglia activation. Our results suggest that regulation of the PTN signaling pathways may constitute new therapeutic opportunities particularly in those neurological disorders characterized by increased PTN cerebral levels and neuroinflammation. Microgliosis (dpeaa)DE-He213 Microglia activation (dpeaa)DE-He213 Midkine (dpeaa)DE-He213 Neuroimmune response (dpeaa)DE-He213 Neuroinflammation (dpeaa)DE-He213 Pleiotrophin (dpeaa)DE-He213 TLR4 (dpeaa)DE-He213 Vicente-Rodríguez, Marta aut Gramage, Esther aut Pita, Jimena aut Pérez-García, Carmen aut Ferrer-Alcón, Marcel aut Uribarri, María aut Ramos, María P. aut Herradón, Gonzalo aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 14(2017), 1 vom: 04. März (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:14 year:2017 number:1 day:04 month:03 https://dx.doi.org/10.1186/s12974-017-0823-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2017 1 04 03
language	English
source	Enthalten in Journal of neuroinflammation 14(2017), 1 vom: 04. März volume:14 year:2017 number:1 day:04 month:03
sourceStr	Enthalten in Journal of neuroinflammation 14(2017), 1 vom: 04. März volume:14 year:2017 number:1 day:04 month:03
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Microgliosis Microglia activation Midkine Neuroimmune response Neuroinflammation Pleiotrophin TLR4
isfreeaccess_bool	true
container_title	Journal of neuroinflammation
authorswithroles_txt_mv	Fernández-Calle, Rosalía @@aut@@ Vicente-Rodríguez, Marta @@aut@@ Gramage, Esther @@aut@@ Pita, Jimena @@aut@@ Pérez-García, Carmen @@aut@@ Ferrer-Alcón, Marcel @@aut@@ Uribarri, María @@aut@@ Ramos, María P. @@aut@@ Herradón, Gonzalo @@aut@@
publishDateDaySort_date	2017-03-04T00:00:00Z
hierarchy_top_id	391784781
id	SPR029107229
language_de	englisch
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author	Fernández-Calle, Rosalía
spellingShingle	Fernández-Calle, Rosalía misc Microgliosis misc Microglia activation misc Midkine misc Neuroimmune response misc Neuroinflammation misc Pleiotrophin misc TLR4 Pleiotrophin regulates microglia-mediated neuroinflammation
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topic_title	Pleiotrophin regulates microglia-mediated neuroinflammation Microgliosis (dpeaa)DE-He213 Microglia activation (dpeaa)DE-He213 Midkine (dpeaa)DE-He213 Neuroimmune response (dpeaa)DE-He213 Neuroinflammation (dpeaa)DE-He213 Pleiotrophin (dpeaa)DE-He213 TLR4 (dpeaa)DE-He213
topic	misc Microgliosis misc Microglia activation misc Midkine misc Neuroimmune response misc Neuroinflammation misc Pleiotrophin misc TLR4
topic_unstemmed	misc Microgliosis misc Microglia activation misc Midkine misc Neuroimmune response misc Neuroinflammation misc Pleiotrophin misc TLR4
topic_browse	misc Microgliosis misc Microglia activation misc Midkine misc Neuroimmune response misc Neuroinflammation misc Pleiotrophin misc TLR4
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title	Pleiotrophin regulates microglia-mediated neuroinflammation
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title_full	Pleiotrophin regulates microglia-mediated neuroinflammation
author_sort	Fernández-Calle, Rosalía
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author_browse	Fernández-Calle, Rosalía Vicente-Rodríguez, Marta Gramage, Esther Pita, Jimena Pérez-García, Carmen Ferrer-Alcón, Marcel Uribarri, María Ramos, María P. Herradón, Gonzalo
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author-letter	Fernández-Calle, Rosalía
doi_str_mv	10.1186/s12974-017-0823-8
title_sort	pleiotrophin regulates microglia-mediated neuroinflammation
title_auth	Pleiotrophin regulates microglia-mediated neuroinflammation
abstract	Background Pleiotrophin (PTN) is a cytokine found highly upregulated in the brain in different disorders characterized by overt neuroinflammation such as neurodegenerative diseases, drug addiction, traumatic injury, and ischemia. In the present work, we have explored whether PTN modulates neuroinflammation and if Toll-like receptor 4 (TLR4), crucial in the initiation of an immune response, is involved. Methods In immunohistochemistry assays, we studied lipopolysaccharide (LPS, 7.5 mg/kg i.p.)-induced changes in glial fibrillary acidic protein (GFAP, astrocyte marker) and ionized calcium-binding adaptor molecule 1 (Iba1, microglia marker) expression in the prefrontal cortex (PFC) and striatum of mice with transgenic PTN overexpression in the brain (PTN-Tg) and in wild-type (WT) mice. Cytokine protein levels were assessed in the PFC by X-MAP technology. The influence of TLR4 signaling in LPS effects in both genotypes was assessed by pretreatment with the TLR4 antagonist (TAK-242, 3.0 mg/kg i.p.). Murine BV2 microglial cells were treated with PTN (0.5 μg/ml) and LPS (1.0 μg/ml) and assessed for the release of nitric oxide (NO). Results We found that LPS-induced microglial activation is significantly increased in the PFC of PTN-Tg mice compared to that of WT mice. The levels of TNF-α, IL-6, and MCP-1 in response to LPS were significantly increased in the PFC of PTN-Tg mice compared to that of WT mice. Pretreatment with TAK-242 efficiently blocked increases in cytokine contents in a similar manner in both genotypes. Concomitant incubation of BV2 cells with LPS and PTN significantly potentiated the production of NO compared to cells only treated with LPS. Conclusions Our findings identify for the first time that PTN is a novel and potent regulator of neuroinflammation. Pleiotrophin potentiates LPS-stimulated microglia activation. Our results suggest that regulation of the PTN signaling pathways may constitute new therapeutic opportunities particularly in those neurological disorders characterized by increased PTN cerebral levels and neuroinflammation. © The Author(s). 2017
abstractGer	Background Pleiotrophin (PTN) is a cytokine found highly upregulated in the brain in different disorders characterized by overt neuroinflammation such as neurodegenerative diseases, drug addiction, traumatic injury, and ischemia. In the present work, we have explored whether PTN modulates neuroinflammation and if Toll-like receptor 4 (TLR4), crucial in the initiation of an immune response, is involved. Methods In immunohistochemistry assays, we studied lipopolysaccharide (LPS, 7.5 mg/kg i.p.)-induced changes in glial fibrillary acidic protein (GFAP, astrocyte marker) and ionized calcium-binding adaptor molecule 1 (Iba1, microglia marker) expression in the prefrontal cortex (PFC) and striatum of mice with transgenic PTN overexpression in the brain (PTN-Tg) and in wild-type (WT) mice. Cytokine protein levels were assessed in the PFC by X-MAP technology. The influence of TLR4 signaling in LPS effects in both genotypes was assessed by pretreatment with the TLR4 antagonist (TAK-242, 3.0 mg/kg i.p.). Murine BV2 microglial cells were treated with PTN (0.5 μg/ml) and LPS (1.0 μg/ml) and assessed for the release of nitric oxide (NO). Results We found that LPS-induced microglial activation is significantly increased in the PFC of PTN-Tg mice compared to that of WT mice. The levels of TNF-α, IL-6, and MCP-1 in response to LPS were significantly increased in the PFC of PTN-Tg mice compared to that of WT mice. Pretreatment with TAK-242 efficiently blocked increases in cytokine contents in a similar manner in both genotypes. Concomitant incubation of BV2 cells with LPS and PTN significantly potentiated the production of NO compared to cells only treated with LPS. Conclusions Our findings identify for the first time that PTN is a novel and potent regulator of neuroinflammation. Pleiotrophin potentiates LPS-stimulated microglia activation. Our results suggest that regulation of the PTN signaling pathways may constitute new therapeutic opportunities particularly in those neurological disorders characterized by increased PTN cerebral levels and neuroinflammation. © The Author(s). 2017
abstract_unstemmed	Background Pleiotrophin (PTN) is a cytokine found highly upregulated in the brain in different disorders characterized by overt neuroinflammation such as neurodegenerative diseases, drug addiction, traumatic injury, and ischemia. In the present work, we have explored whether PTN modulates neuroinflammation and if Toll-like receptor 4 (TLR4), crucial in the initiation of an immune response, is involved. Methods In immunohistochemistry assays, we studied lipopolysaccharide (LPS, 7.5 mg/kg i.p.)-induced changes in glial fibrillary acidic protein (GFAP, astrocyte marker) and ionized calcium-binding adaptor molecule 1 (Iba1, microglia marker) expression in the prefrontal cortex (PFC) and striatum of mice with transgenic PTN overexpression in the brain (PTN-Tg) and in wild-type (WT) mice. Cytokine protein levels were assessed in the PFC by X-MAP technology. The influence of TLR4 signaling in LPS effects in both genotypes was assessed by pretreatment with the TLR4 antagonist (TAK-242, 3.0 mg/kg i.p.). Murine BV2 microglial cells were treated with PTN (0.5 μg/ml) and LPS (1.0 μg/ml) and assessed for the release of nitric oxide (NO). Results We found that LPS-induced microglial activation is significantly increased in the PFC of PTN-Tg mice compared to that of WT mice. The levels of TNF-α, IL-6, and MCP-1 in response to LPS were significantly increased in the PFC of PTN-Tg mice compared to that of WT mice. Pretreatment with TAK-242 efficiently blocked increases in cytokine contents in a similar manner in both genotypes. Concomitant incubation of BV2 cells with LPS and PTN significantly potentiated the production of NO compared to cells only treated with LPS. Conclusions Our findings identify for the first time that PTN is a novel and potent regulator of neuroinflammation. Pleiotrophin potentiates LPS-stimulated microglia activation. Our results suggest that regulation of the PTN signaling pathways may constitute new therapeutic opportunities particularly in those neurological disorders characterized by increased PTN cerebral levels and neuroinflammation. © The Author(s). 2017
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title_short	Pleiotrophin regulates microglia-mediated neuroinflammation
url	https://dx.doi.org/10.1186/s12974-017-0823-8
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author2	Vicente-Rodríguez, Marta Gramage, Esther Pita, Jimena Pérez-García, Carmen Ferrer-Alcón, Marcel Uribarri, María Ramos, María P. Herradón, Gonzalo
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