title: Glucocorticoids induced the production and gene expression of IL-1alpha through AP-1 and partially NF-kappaB activation in murine epidermal cells.
abstract: To investigate the mechanism of the glucocorticoids-induced augmentation of skin response, we have recently reported the modulatory effect of glucocorticoids on the regulation of cytokines production in keratinocytes stimulated with various chemicals in vitro through both NF-kappaB and AP-1 activation. Further to clarify the mechanism in the glucocorticoids-induced augmentation of cytokines production from keratinocytes, we examined the effect of glucocorticoids to keratinocytes without chemical stimulation. Glucocorticoids 10(-4) M inhibited the production of IL-1alpha from Pam 212 cells. However, lower concentration (10(-8)-10(-10) M) of glucocorticoids significantly enhanced the production of IL-1alpha by Pam 212 cells at both the protein and mRNA levels. In contrast, glucocorticoids had no effect on the production of either TNF-alhpa, IL-6, nor GM-CSF by Pam 212 cells cultured for 6 h. Electrophoretic mobility shift assays (EMSA) revealed that 10(-10)-10(-12) M glucocorticoids induced the NF-kappaB activation in Pam 212 cells, however, augmented AP-1 activation by 10(-8)-10(-10) M of glucocorticoids was observed in Pam 212 cells. Furthermore, pyrrolidine dithiocarbamate (PDTC) partially inhibited the IL-1alpha production and completely inhibited NF-kappaB expression by Pam 212 cells. On the other hand, MAP-kinase inhibitors (PD98059, SB202190) completely abrogated not only AP-1 activation but the low concentration glucocorticoids-induced IL-1alpha production. These data indicated that lower concentration of glucocorticoids induced the augmentation of IL-1alpha production from keratinocytes mediated through the AP-1 pathway and partially through NF-kappaB pathway.
authors.affiliation: Department of Dermatology and Immunodermatology, Graduate School, Tokyo Medical and Dental University, Japan.
authors.forename: Sherif
authors.initials: S
authors.lastname: Awad
authors.forename: Hiroo
authors.initials: H
authors.lastname: Yokozeki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Ken
authors.initials: K
authors.lastname: Igawa
authors.forename: Kazuya
authors.initials: K
authors.lastname: Minatohara
authors.forename: Takahiro
authors.initials: T
authors.lastname: Satoh
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Nishioka
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002460:Cell Line; D004587:Electrophoresis, Agar Gel; D024202:Electrophoretic Mobility Shift Assay; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006854:Hydrocortisone / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D013859:Thiocarbamates / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D007375:Interleukin-1; D015850:Interleukin-6; D016328:NF-kappa B; D011725:Pyridines; D011759:Pyrrolidines; D012333:RNA, Messenger; D013859:Thiocarbamates; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C020972:pyrrolidine dithiocarbamic acid; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D006854:Hydrocortisone