title: A role of mitogen and stress-activated protein kinase 1/2 in survival of lipopolysaccharide-stimulated RAW 264.7 macrophages.
abstract: The effect of inhibition of mitogen and stress-activated protein kinases 1/2 (MSK1/2) on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells was investigated. Pretreatment with Ro 31-8220, an inhibitor of MSK1/2, induced cell death in LPS-stimulated RAW 264.7 cells. In contrast, calphostin C, another inhibitor of protein kinase C, did not cause cell death. Cell death was not mediated by the release of pro-inflammatory mediators from LPS-stimulated RAW 264.7 cells. Cell death was accompanied by DNA fragmentation and annexin V binding, suggesting apoptotic cell death. Further, several caspase inhibitors did not prevent LPS-induced cell death of Ro 31-8220-pretreated RAW 264.7 cells. Nuclear translocation of apoptosis-inducing factor (AIF) was detected in Ro 31-8220-pretreated cells after LPS stimulation. Cell death was due to mitochondrial damage. Ro 31-8220 exclusively inhibited the phosphorylation of cAMP-responsive element binding protein (CREB), a substrate of MSK1/2. RAW 264.7 cells transfected with the dominant-negative MSK1 clones underwent cell death in response to LPS. Hence, it was suggested that MSK1/2 might play a critical role in the survival of LPS-stimulated RAW 264.7 cells.
authors.affiliation: Department of Microbiology and Immunology and Research Center for Infectious Disease, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan.
authors.forename: Mya Mya
authors.initials: MM
authors.lastname: Mu
authors.forename: Naoki
authors.initials: N
authors.lastname: Koide
authors.forename: Ferdaus
authors.initials: F
authors.lastname: Hassan
authors.forename: Shamima
authors.initials: S
authors.lastname: Islam
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ito
authors.forename: Isamu
authors.initials: I
authors.lastname: Mori
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Yoshida
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokochi
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D051033:Apoptosis Inducing Factor; D061945:Caspase Inhibitors; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D002470:Cell Survival; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D053938:DNA Fragmentation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005420:Flavoproteins / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology*; D008264:Macrophages / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D009281:Naphthalenes / Q000494:pharmacology; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism*
chemical_list: D017304:Annexin A5; D051033:Apoptosis Inducing Factor; D061945:Caspase Inhibitors; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D005420:Flavoproteins; D007211:Indoles; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D009281:Naphthalenes; C494830:AIFM1 protein, mouse; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C485459:Rps6ka4 protein, mouse; C116919:mitogen and stress-activated protein kinase 1; C058819:calphostin C; C064758:Ro 31-8220