PMID- 12420106 OWN - NLM STAT- MEDLINE DCOM- 20030716 LR - 20131121 IS - 0340-3696 (Print) IS - 0340-3696 (Linking) VI - 294 IP - 8 DP - 2002 Nov TI - Upregulation of interleukin-18 expression in mouse primary keratinocytes induced to differentiate by calcium. PG - 370-6 AB - 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. FAU - Kong, Juan AU - Kong J AD - Department of Medicine, University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, USA. FAU - Li, Yan Chun AU - Li YC LA - eng GR - DK59327/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20021008 PL - Germany TA - Arch Dermatol Res JT - Archives of dermatological research JID - 8000462 RN - 0 (Interleukin-18) RN - 63231-63-0 (RNA) RN - EC 2.7.11.13 (Protein Kinase C) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Calcium/*pharmacology MH - Cell Differentiation/drug effects MH - Cells, Cultured MH - Enzyme Activation/drug effects/physiology MH - Immunohistochemistry MH - Interleukin-18/*metabolism MH - Keratinocytes/*cytology/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Protein Kinase C/metabolism MH - RNA/biosynthesis MH - Skin/metabolism MH - Up-Regulation EDAT- 2002/11/07 04:00 MHDA- 2003/07/17 05:00 CRDT- 2002/11/07 04:00 PHST- 2002/04/24 00:00 [received] PHST- 2002/07/23 00:00 [revised] PHST- 2002/08/24 00:00 [accepted] PHST- 2002/11/07 04:00 [pubmed] PHST- 2003/07/17 05:00 [medline] PHST- 2002/11/07 04:00 [entrez] AID - 10.1007/s00403-002-0348-5 [doi] PST - ppublish SO - Arch Dermatol Res. 2002 Nov;294(8):370-6. doi: 10.1007/s00403-002-0348-5. Epub 2002 Oct 8.