Mitogen-activated protein kinases are involved in tumor necrosis factor alpha production in macrophages infected with Orientia tsutsugamushi.
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.
Yun
Ji-Hyun
JH
Department of Microbiology, School of Medicine, BK21 Program, and Institute of Medical Science, Cheju National University, Jeju 690-756, Republic of Korea.
Koo
Jung-Eun
JE
Koh
Young-Sang
YS
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
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