IL-1F5, -F6, -F8, and -F9: a novel IL-1 family signaling system that is active in psoriasis and promotes keratinocyte antimicrobial peptide expression.
IL-1F6, IL-1F8, and IL-1F9 and the IL-1R6(RP2) receptor antagonist IL-1F5 constitute a novel IL-1 signaling system that is poorly characterized in skin. To further characterize these cytokines in healthy and inflamed skin, we studied their expression in healthy control, uninvolved psoriasis, and psoriasis plaque skin using quantitative RT-PCR and immunohistochemistry. Expression of IL-1F5, -1F6, -1F8, and -1F9 were increased 2 to 3 orders of magnitude in psoriasis plaque versus uninvolved psoriasis skin, which was supported immunohistologically. Moreover, treatment of psoriasis with etanercept led to significantly decreased IL-1F5, -1F6, -1F8, and -1F9 mRNAs, concomitant with clinical improvement. Similarly increased expression of IL-1F5, -1F6, -1F8, and -1F9 was seen in the involved skin of two mouse models of psoriasis. Suggestive of their importance in inflamed epithelia, IL-1α and TNF-α induced IL-1F5, -1F6, -1F8, and -1F9 transcript expression by normal human keratinocytes. Microarray analysis revealed that these cytokines induce the expression of antimicrobial peptides and matrix metalloproteinases by reconstituted human epidermis. In particular, IL-1F8 increased mRNA expression of human β-defensin (HBD)-2, HBD-3, and CAMP and protein secretion of HBD-2 and HBD-3. Collectively, our data suggest important roles for these novel cytokines in inflammatory skin diseases and identify these peptides as potential targets for antipsoriatic therapies.
Department of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA.
Andrew
A
Johnston
Xianying
X
Xing
Andrew M
AM
Guzman
MaryBeth
M
Riblett
Candace M
CM
Loyd
Nicole L
NL
Ward
Christian
C
Wohn
Errol P
EP
Prens
Frank
F
Wang
Lisa E
LE
Maier
Sewon
S
Kang
John J
JJ
Voorhees
James T
JT
Elder
Johann E
JE
Gudjonsson
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004817:Epidermis / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000502:physiology*; D007378:Interleukins / Q000502:physiology*; D015603:Keratinocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011565:Psoriasis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
D023181:Antimicrobial Cationic Peptides; C508586:IL36A protein, human; C508588:IL36B protein, human; C508589:IL36G protein, human; C122187:IL36RN protein, human; C478197:Il36rn protein, mouse; D007375:Interleukin-1; D007378:Interleukins; D020782:Matrix Metalloproteinases
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