PMID- 11125306 OWN - NLM STAT- MEDLINE DCOM- 20010308 LR - 20061115 IS - 1148-5493 (Print) IS - 1148-5493 (Linking) VI - 11 IP - 4 DP - 2000 Dec TI - Regulation of interleukin-18 (IL-18) expression in keratinocytes (HaCaT): implications for early wound healing. PG - 626-33 AB - Keratinocytes display a high basal level expression of IL-18. Tumor necrosis factor-alpha (TNF-alpha) mediated a large decrease in IL-18 mRNA levels in the human keratinocyte cell line HaCaT, which was accompanied by a subsequent accumulation of IL-18 protein in the cell culture supernatants, which was shown to be biologically active. By contrast, epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha), respectively, strongly decreased IL-18 mRNA expression in HaCaT keratinocytes in the absence of IL-18 protein release from the cells. Notably, a pre-treatment of the cells with EGF, or TGF-alpha clearly attenuated TNF-alpha-induced IL-18 protein, release and bioactivity. For the in vivo situation of cutaneous wound repair, we observed an increase in IL-18 protein, 10 hours post-wounding, that closely correlated to infiltration of neutrophils which are known as producers of TNF-alpha. Our data suggest that bioactive IL-18 might be tightly counter-regulated by platelet- and neutrophil-derived factors at the onset of repair. FAU - Kampfer, H AU - Kampfer H AD - Zentrum der Pharmakologie, Klinikum der Johann Wolfgang goethe-Universitat, Frankfurt am Main, Germany. FAU - Muhl, H AU - Muhl H FAU - Manderscheid, M AU - Manderscheid M FAU - Kalina, U AU - Kalina U FAU - Kauschat, D AU - Kauschat D FAU - Pfeilschifter, J AU - Pfeilschifter J FAU - Frank, S AU - Frank S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - France TA - Eur Cytokine Netw JT - European cytokine network JID - 9100879 RN - 0 (Interleukin-18) RN - 0 (RNA, Messenger) RN - 0 (Transforming Growth Factor alpha) RN - 0 (Tumor Necrosis Factor-alpha) RN - 62229-50-9 (Epidermal Growth Factor) SB - IM MH - Blood Platelets/immunology MH - Cell Line MH - Epidermal Growth Factor/*immunology MH - Gene Expression Regulation MH - Humans MH - Interleukin-18/*genetics/immunology MH - Keratinocytes/drug effects/*immunology MH - Neutrophil Infiltration/immunology MH - Neutrophils/immunology MH - RNA, Messenger/analysis MH - Transforming Growth Factor alpha/*immunology MH - Tumor Necrosis Factor-alpha/*immunology MH - Wound Healing/*immunology EDAT- 2000/12/23 11:00 MHDA- 2001/03/10 10:01 CRDT- 2000/12/23 11:00 PHST- 2000/12/23 11:00 [pubmed] PHST- 2001/03/10 10:01 [medline] PHST- 2000/12/23 11:00 [entrez] PST - ppublish SO - Eur Cytokine Netw. 2000 Dec;11(4):626-33.