title: Upregulation of interleukin-18 expression in mouse primary keratinocytes induced to differentiate by calcium.
abstract: Interleukin-18 (IL-18) is an immunomodulatory cytokine that stimulates interferon-gamma production by T helper cells. Recently, basal keratinocytes have been shown to constitutively express IL-18, and IL-18 expression increases in the suprabasal keratinocytes in psoriatic lesions. In the study reported here we showed that in mouse epidermis, IL-18 immunoreactivity was markedly increased in the granular and cornified layers. To further investigate whether differentiated keratinocytes synthesize more IL-18, we examined the expression of mouse IL-18 in primary mouse keratinocytes induced to differentiate by calcium, an in vitro cell culture system mimicking keratinocyte differentiation in the epidermis. We demonstrated that IL-18 mRNA and protein in cultured keratinocytes were increased by calcium treatment in a time- and dose-dependent manner. The upregulation of IL-18 was associated with an increase in keratinocyte differentiation markers, and was dependent on the synthesis of new RNAs and proteins. However, the IL-18 protein in the cytoplasm was predominantly in the precursor form, and no increase in IL-18 activity was detected in the culture medium treated with calcium. Furthermore, blocking the calcium-induced keratinocyte differentiation with protein kinase C inhibitor inhibited the upregulation of IL-18 expression. These findings suggest that IL-18 is synthesized in keratinocytes mainly in the inactive precursor form, and its expression is upregulated as basal keratinocytes differentiate in the epidermis.
authors.affiliation: Department of Medicine, University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Kong
authors.forename: Yan Chun
authors.initials: YC
authors.lastname: Li
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D020382:Interleukin-18 / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011493:Protein Kinase C / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis; D012867:Skin / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D020382:Interleukin-18; D012313:RNA; D011493:Protein Kinase C; D002118:Calcium