The pro-inflammatory cytokine IL-22 up-regulates keratin 17 expression in keratinocytes via STAT3 and ERK1/2.
BACKGROUND
To investigate the regulation of K17 expression by the pro-inflammatory cytokine IL-22 in keratinocytes and its important role in our previously hypothesized "K17/T cell/cytokine autoimmune loop" in psoriasis.


METHODS
K17 expression was examined in the IL-22-treated keratinocytes by real-time quantitative PCR, ELISA, Western blot and Immunofluorescence. In addition, the signaling pathways involved in K17 regulation were investigated with related inhibitors and siRNAs. In addition, K17 expression was examined in the epidermis of IL-22-injected mouse skin.


RESULTS
IL-22-induced K17 expression was confirmed in keratinocytes and the epidermis of IL-22-injected mouse skin at both mRNA and protein levels, which is an important complement to the autoimmune loop. We further investigated the regulatory mechanisms and found that both STAT3 and ERK1/2 were involved in the up-regulation of K17 expression induced by IL-22.


CONCLUSIONS
IL-22 up-regulates K17 expression in keratinocytes in a dose-dependent manner through STAT3- and ERK1/2-dependent mechanisms. These findings indicated that IL-22 was also involved in the K17/T cell/cytokine autoimmune loop and may play an important role in the progression of psoriasis.
Department of Dermatology, Fourth Military Medical University, Xijing Hospital, Xi'an, People's Republic of China.
Wei
W
Zhang
Erle
E
Dang
Xiaowei
X
Shi
Liang
L
Jin
Zhenzhen
Z
Feng
Lei
L
Hu
Yan
Y
Wu
Gang
G
Wang
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D000078404:Epidermal Cells; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D020381:Interleukin-17 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D053537:Keratin-17 / Q000378:metabolism*; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D034741:RNA, Small Interfering / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*; D000097043:Interleukin-22
D016207:Cytokines; D048049:Extracellular Signal-Regulated MAP Kinases; D018836:Inflammation Mediators; D007371:Interferon-gamma; D020381:Interleukin-17; D007378:Interleukins; D053537:Keratin-17; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D000097043:Interleukin-22