Interleukin 4-induced proliferation in normal human keratinocytes is associated with c-myc gene expression and inhibited by genistein.
We studied the effect of IL-4 on the proliferation of cultured normal human keratinocytes. Keratinocyte proliferation was stimulated by IL-4 and inhibited by anti-IL-4 antibody in a concentration-dependent manner. Anti-IL-6 antibody did not inhibit normal human keratinocyte proliferation, suggesting that the IL-4 could directly induce proliferation of these cells. IL-4 significantly induced cell cycle G0/G1 to S phase progression. The keratinocyte proliferation by IL-4 was mediated through one of the growth control genes, c-myc protooncogene. The expression of c-myc mRNA was significantly increased after IL-4 treatment of the keratinocytes, suggesting that c-myc plays a key role in the control of proliferation. The signal transduction pathways induced by IL-4 in the keratinocytes were studied with inhibitors of signal transduction. Genistein, a tyrosine kinase inhibitor, suppressed the level of the induced c-myc mRNA expression, but H7, a serine/threonine kinase inhibitor, and okadaic acid, a protein phosphatase 1 and 2A inhibitor, did not block the induced c-myc gene expression. Taken together, these results suggest that IL-4 stimulates the proliferation of keratinocytes in vitro by promoting a transition from G0/G1 to S phase of the cell cycle. Induction of c-myc after IL-4 treatment could indicate an important role for c-myc in the proliferation of keratinocytes. Our observations also suggest that tyrosine kinases may be involved in IL-4-induced proliferation.
Yang
Y
Y
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon, Republic of Korea.
Yoo
H M
HM
Choi
I
I
Pyun
K H
KH
Byun
S M
SM
Ha
H
H
D001483:Base Sequence; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division; D015870:Gene Expression; D016259:Genes, myc; D019833:Genistein; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology*; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D012016:Reference Values; D014158:Transcription, Genetic / Q000187:drug effects
D006131:Growth Inhibitors; D015850:Interleukin-6; D007529:Isoflavones; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D015847:Interleukin-4; D019833:Genistein