International immunopharmacology · 2019
Acitretin inhibits IL-17A-induced IL-36 expression in keratinocytes by down-regulating IκBζ.
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Tu Jie, Yin Zhi, Guo Jing, He Fang, Long FangYuan, Yin ZhiQiang
Аннотация
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.
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.