Insulin-like growth factor II induces interleukin-6 expression via NFkappaB activation in psoriasis.
IGF-II is known to induce the growth of keratinocytes and the level was significantly elevated in the tissue fluid of psoriatic lesion. However, the role of IGF-II in psoriasis is not well defined. Because an inflammatory cytokine, interleukin-6 (IL-6) is overexpressed in psoriatic lesions, we explored whether IGF-II has some role in psoriasis through induction of IL-6. Therefore, the expression of IL-6 was analyzed after treatment of IGF-II in primary cultured psoriatic cells and human keratinocyte cell line, HaCaT. We found that IGF-II induced the IL-6 mRNA expression significantly. To investigate the inducing mechanism of IL-6 by IGF-II, we examined the promoter activity of IL-6 and the DNA binding activity of NFkappaB, a strong regulator of IL-6. Interestingly, IL-6 promoter activity and the binding activity of NFkappaB were remarkably increased by IGF-II. Western blot data that IkappaB was reduced by IGF-II significantly suggest that NFkappaB activation by IGF-II may be mediated through the downregulation of IkappaB. Therefore, these results suggest a novel role of IGF-II in psoriasis possibly by inducing IL-6 through the activation of NFkappaB mediated by downregulation of IkappaB.
Kwon
Y W
YW
Department of Molecular Biology, Pusan National University, Pusan, 609-735, Korea.
Jang
E R
ER
Lee
Y M
YM
Kim
Y S
YS
Kwon
K S
KS
Jang
H S
HS
Oh
C K
CK
Kim
K W
KW
D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011565:Psoriasis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics
D017931:DNA Primers; D020672:I-kappa B Proteins; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II; D004247:DNA