title: Pro-survival effects of JNK and p38 MAPK pathways in LPS-induced activation of BV-2 cells.
abstract: Identifying MAPK pathways and understanding their role in microglial cells may be crucial for understanding the pathogenesis of neurodegenerative diseases since activated microglia could contribute to the progressive nature of neurodegeneration. In this study we show that the JNK pathway plays an important role in the survival of resting microglia BV-2 cells, as evidenced by Annexin-V positive staining and caspase-3 activation in cells treated with the specific JNK inhibitor SP600125. During LPS-induced activation of BV-2 cells inhibition of the p38 and JNK pathways with SB203580 and SP600125, respectively, results in apoptosis as detected by apoptotic markers. In the presence SP600125 the phosphorylation of p38 was significantly increased both in control and LPS-activated BV-2 cells. This suggests that the pro-survival role of JNK is possible due to its abrogation of a potentially apoptotic signal mediated by p38 MAPK pathway. Furthermore, inhibition of the p38 MAPK pathway during LPS-induced activation of BV-2 cells resulted in an increased phosphorylation of c-Jun, suggesting that the pro-survival effect of p38 MAPK during inflammatory conditions involves the JNK pathway. In conclusion, the results of this study demonstrate that both the JNK and p38 MAPK pathways possess anti-apoptotic functions in the microglial cell line BV-2 during LPS-induced activation.
authors.affiliation: Stockholm University, Department of Neurochemistry, Stockholm, Sweden. nina@neurochem.su.se
authors.forename: Christina
authors.initials: C
authors.lastname: Svensson
authors.forename: Kristin
authors.initials: K
authors.lastname: Part
authors.forename: Kai
authors.initials: K
authors.lastname: Künnis-Beres
authors.forename: Margit
authors.initials: M
authors.lastname: Kaldmäe
authors.forename: Sandra Zetterström
authors.initials: SZ
authors.lastname: Fernaeus
authors.forename: Tiit
authors.initials: T
authors.lastname: Land
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis; D002460:Cell Line; D002470:Cell Survival; D007249:Inflammation / Q000201:enzymology / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000201:enzymology / Q000276:immunology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000873:Anthracenes; D008070:Lipopolysaccharides; D047428:Protein Kinase Inhibitors; C432165:pyrazolanthrone; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4