Regulation of interleukin-18 (IL-18) expression in keratinocytes (HaCaT): implications for early wound healing.
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.
Kämpfer
H
H
Zentrum der Pharmakologie, Klinikum der Johann Wolfgang goethe-Universität, Frankfurt am Main, Germany.
Mühl
H
H
Manderscheid
M
M
Kalina
U
U
Kauschat
D
D
Pfeilschifter
J
J
Frank
S
S
D001792:Blood Platelets / Q000276:immunology; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics* / Q000276:immunology; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology*; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D016211:Transforming Growth Factor alpha / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D014945:Wound Healing / Q000276:immunology*
D020382:Interleukin-18; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D014409:Tumor Necrosis Factor-alpha; D004815:Epidermal Growth Factor