IL-22可诱导角质形成细胞双调蛋白表达促进银屑病发病

IL-22 regulates positively amphiregulin expression of keratinocytes involved in psoriasis

目的研究IL-22对角质形成细胞系HaCaT细胞双调蛋白(amphiregulin,AREG)表达的调控,了解其在寻常型银屑病(PsV)中的作用。方法收集PsV患者皮损( n =26)和健康人皮肤组织( n =15),RT-qPCR检测IL-22、 IL-22R1 、 IL-22BP 及AREG的表达并分析其相关性。用IL-22(20 ng/mL)及其可溶型受体IL-22BP(20 ng/mL)干预培养HaCaT细胞24 h,RT-qPCR及Western blot检测AREG的表达变化。结果PsV患者皮损IL-22(P<0.001)、 IL-22R1 (P<0.001)及AREG(P<0.01)的mRNA表达分别高于健康人皮肤36倍、24倍和15倍。PsV皮损的 IL-22 与AREG mRNA水平密切相关( r =0.49,P<0.05)。IL-22干预时,HaCaT细胞AREG mRNA表达升高22倍(P<0.01),蛋白表达亦明显升高(P<0.01)。IL-22BP则抑制了IL-22的这一功能(P<0.05)。结论IL-22可能通过刺激角质形成细胞增强AREG的表达参与银屑病的发病,IL-22BP可作为阻断剂抑制这种增强作用,可能在银屑病的治疗中发挥作用。

Objective To investigate the effect of IL-22 on the expression of Amphiregulin (AREG) in HaCaT and further understand its role in psoriasis vulgaris (PsV). Methods The mRNA expressions of IL-22,IL-22R1,IL-22BP and AREG were detected by RT-qPCR in PsV lesions ( n =26) and healthy control (HC) skin specimens ( n =15). RT-qPCR and Western blot were applied to detect the expression of AREG in HaCaT cells stimulated with IL-22 (20 ng/mL) and its soluble receptor IL-22BP (20 ng/mL) for 24 h. Results The mRNA expressions of IL-22 ( P <0.001),IL-22R1 ( P <0.001) and AREG ( P <0.01) were significantly increased respectively by 36 times,24 times and 15 times in PsV compared with those in HC. In addition,there were positive correlations between the mRNA levels of AREG and IL-22 ( r =0.49, P <0.05). IL-22 could upregulate the mRNA level of AREG by 22 times and protein expression by 6 times in HaCaT cells ( P <0.01). IL-22BP could inhibit the effect of IL-22 ( P <0.05). Conclusion IL-22 may regulate positively amphiregulin expression of keratinocytes involved in psoriasis,and IL-22BP may inhibit this role as a blocker in treating psoriasis.