title: Mitogen-activated protein kinases are involved in tumor necrosis factor alpha production in macrophages infected with Orientia tsutsugamushi.
abstract: Orientia tsutsugamushi, an obligatory intracellular bacterium, is the causative agent of scrub typhus. Here the role of MAPK in TNF-alpha production in macrophages after infection with O. tsutsugamushi has been investigated. ERK1/2, JNK, and p38 MAPK became phosphorylated in Orientia-stimulated macrophages. Selective inhibitors of MAPK cascades could all significantly reduce Orientia-stimulated TNF-alpha production. Orientia-stimulated TNF-alpha production via p38 and JNK pathways was regulated by a post-transcriptional mechanism, whereas the ERK pathway mainly controlled the transcriptional step of TNF-alpha gene expression during infection. In conclusion, our data indicate that MAPK signaling is required to induce maximal TNF-alpha production in macrophages during Orientia infection.
authors.affiliation: Department of Microbiology, School of Medicine, BK21 Program, and Institute of Medical Science, Cheju National University, Jeju 690-756, Republic of Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Yun
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Koo
authors.forename: Young-Sang
authors.initials: YS
authors.lastname: Koh
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D005786:Gene Expression Regulation; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D007739:L Cells; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D008809:Mice, Inbred C3H; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D012285:Orientia tsutsugamushi / Q000472:pathogenicity*; D012612:Scrub Typhus / Q000382:microbiology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases