Jie Tu1, Zhi Yin1, Jing Guo2, Fang He1, FangYuan Long1, ZhiQiang Yin3. 1. Department of Dermatology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. 2. Department of Dermatology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Deparment of Dermatology, Zhenjiang First People's Hospital, Zhenjiang, China. 3. Department of Dermatology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. Electronic address: yzq2802@sina.com.
Abstract
BACKGROUND: IL-36 plays a critical role in aggravating psoriatic inflammation, which is significantly elevated in generalized pustular psoriasis (GPP) compared to psoriasis vulgaris. It is well known that acitretin brings about a rapid and significant effect on the treatment of GPP but not psoriasis vulgaris, whereas the quick therapeutic mechanism of acitretin in GPP has not been fully clarified. OBJECTIVES: We conducted this study to investigate whether acitretin interferes IL-36 expression in keratinocytes. METHOD: We used 100 ng/mL IL-17A and/or various doses of acitretin (0, 0.1, 1, 10 μmol/L) to treat cultured HaCaT cells. We performed Real-time quantitative PCR and ELISA to detect gene and protein expression of IL-36 cytokines, real-time quantitative PCR and Western blot to examine IκBζ. Imiquimod (IMQ)-induced psoriasis-like mouse model was established to evaluate effect of gastrointestinal administrated acitretin. Immunohistochemistry was conducted for effect assessment. RESULTS: Acitretin significantly down-regulated expression of IL-36β and IL-36γ induced by IL-17A stimulation at both gene and protein levels in HaCaT cells. Acitretin alone had no obvious effect on IL-36 expression in keratinocytes. In IMQ + acitretin group, the skin lesion severity was slightly relieved, however, immunohistochemistry showed IL-36β and IL-36γ expression in keratinocytes significantly declined in comparison with IMQ group. IL-17A stimulation induced significantly IκBζ expression in HaCaT cells, which could be inhibited by acitretin. CONCLUSION: Acitretin inhibits IL-36 expression induced by IL-17A stimulation in keratinocytes by down-regulating IκBζ, and acitretin significantly inhibits keratinocytes-expressed IL-36β and IL-36γ in psoriasis-like mouse model, which reveals a new possible mechanism of the notable and quick therapeutic action of acitretin on GPP.
BACKGROUND: IL-36 plays a critical role in aggravating psoriatic inflammation, which is significantly elevated in generalized pustular psoriasis (GPP) compared to psoriasis vulgaris. It is well known that acitretin brings about a rapid and significant effect on the treatment of GPP but not psoriasis vulgaris, whereas the quick therapeutic mechanism of acitretin in GPP has not been fully clarified. OBJECTIVES: We conducted this study to investigate whether acitretin interferes IL-36 expression in keratinocytes. METHOD: We used 100 ng/mL IL-17A and/or various doses of acitretin (0, 0.1, 1, 10 μmol/L) to treat cultured HaCaT cells. We performed Real-time quantitative PCR and ELISA to detect gene and protein expression of IL-36 cytokines, real-time quantitative PCR and Western blot to examine IκBζ. Imiquimod (IMQ)-induced psoriasis-like mouse model was established to evaluate effect of gastrointestinal administrated acitretin. Immunohistochemistry was conducted for effect assessment. RESULTS:Acitretin significantly down-regulated expression of IL-36β and IL-36γ induced by IL-17A stimulation at both gene and protein levels in HaCaT cells. Acitretin alone had no obvious effect on IL-36 expression in keratinocytes. In IMQ + acitretin group, the skin lesion severity was slightly relieved, however, immunohistochemistry showed IL-36β and IL-36γ expression in keratinocytes significantly declined in comparison with IMQ group. IL-17A stimulation induced significantly IκBζ expression in HaCaT cells, which could be inhibited by acitretin. CONCLUSION:Acitretin inhibits IL-36 expression induced by IL-17A stimulation in keratinocytes by down-regulating IκBζ, and acitretin significantly inhibits keratinocytes-expressed IL-36β and IL-36γ in psoriasis-like mouse model, which reveals a new possible mechanism of the notable and quick therapeutic action of acitretin on GPP.