Interleukin-17 and Interleukin-22 Induced Proinflammatory Cytokine Production in Keratinocytes via Inhibitor of Nuclear Factor kappaB Kinase-alpha Expression.
- Author:
Kyung Ah CHO
1
;
Jin Young KIM
;
So Youn WOO
;
Hyun Jeong PARK
;
Kyung Ho LEE
;
Chi Un PAE
Author Information
- Publication Type:Original Article
- Keywords: Cell differentiation; IKK alpha; Inflammation; Interleukin-17; Interleukin-22; Keratinocytes
- MeSH: Animals; Calcium; Cell Culture Techniques; Cell Cycle; Cell Cycle Checkpoints; Cell Differentiation; Ear; Epidermis; Humans; I-kappa B Kinase; Inflammation; Interleukin-17; Interleukins; Keratinocytes; Mice; Psoriasis; Skin; Th17 Cells
- From:Annals of Dermatology 2012;24(4):398-405
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND: The pathogenesis of psoriasis may involve the interleukin (IL)-23 and Th17-mediated immune responses. Th17 cells secret IL-17 and IL-22, which mediates dermal inflammation and acanthosis. OBJECTIVE: As inhibitor of nuclear factor kappaB kinase-alpha (IKKalpha) has been previously identified as a primary regulator of keratinocyte differentiation and proliferation, we proposed that IL-17 and IL-22 might affect keratinocyte differentiation by changing the expression of IKKalpha. METHODS: We employed HaCaT cells maintained culture medium at a low calcium concentration (0.06 mM) and induced differentiation by switching to the high concentration (2.8 mM) media with IL-17 or IL-22, then compared the IKKalpha expression and the cell cycle. We employed reconstituted human epidermal skin (Neoderm) and mice ears for the in vivo studies. RESULTS: Elevated calcium concentration induced IKKalpha expression and terminal differentiation with cell cycle arrest in HaCaT cell cultures. Moreover, IL-17 and IL-22 treatment also induced IKKalpha in HaCaT cells and reconstituted human epidermis. IKKalpha induction was also noted, following the injection of IL-17 and IL-22 into mice ears. CONCLUSION: Although the induction of IKKalpha was accompanied by keratinocyte differentiation, IL-17 and IL-22 did not affect calcium-mediated differentiation or the cell cycle. Rather, IL-17 and IL-22 appear to contribute to the inflammation occurring via the induction of IKKalpha from keratinocytes or skin layers.
