title: MAPK signaling pathways modulate IL-1beta expression in human keratinocytes.
abstract: The signaling pathways that modulate IL-1beta expression in human keratinocytes have not been well defined. We have previously shown that TCDD-stimulated AhR-dependent IL-1beta expression in human keratinocytes is due to posttranscriptional regulation involving mRNA stabilization. Since TCDD activates a variety of cellular signaling pathways such as PKC, JNK, and ERK, we investigated these pathways to determine their roles in TCDD-stimulated IL-1beta expression in the human keratinocyte cell line SCC-12F. In this study, we used specific signaling inhibitors to show that ERK and JNK, but not transglutaminase, PKC, or p38, signaling modulate IL-1beta expression. In addition, we show that ERK is constitutively active and unaffected by TCDD treatment and differentiation, while the JNK signaling pathway is modulated by TCDD in an AhR-dependent manner. Thus, both the ERK and JNK MAPK pathways are necessary for IL-1beta expression in TCDD-stimulated human keratinocytes, however, they act at different levels to modulate IL-1beta expression.
authors.affiliation: Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, MO, USA.
authors.forename: Derek V
authors.initials: DV
authors.lastname: Henley
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Bellone
authors.forename: Debbie A
authors.initials: DA
authors.lastname: Williams
authors.forename: Mary F
authors.initials: MF
authors.lastname: Ruh
mesh_terms: D002461:Cell Line, Transformed; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D048031:JNK Mitogen-Activated Protein Kinases; D015603:Keratinocytes / Q000201:enzymology / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism / Q000633:toxicity; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D007375:Interleukin-1; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases