Lipoxin A4 Ameliorates Imiquimod-Induced Psoriasis-Like Dermatitis via Promoting the Regression of Inflammation

Feng Hu,1,2,* Zilu Qu,1,2,* Kai Chen,1,2 Ping Zhang,1 Bei Wang,1 Ruili Jiang,1 Yuyue Zuo,1 Ping Xia,1,* Hongxiang Chen3,4,* 1Department of Dermatology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Hubei Province & Key Laboratory of Skin Infection and Immunity, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Department of Dermatology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518052, People’s Republic of China; 4Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongxiang Chen, Huazhong University of Science and Technology Union Shenzhen Hospital, No. 89, Taoyuan Road, Nanshan District, Shenzhen, 518052, People’s Republic of China, Tel +86 13871022932, Email hongxiangchen@hotmail.com Ping Xia, Email alicexiaping@gmail.comIntroduction: As a mediator of inflammation resolution, lipoxin A4 (LXA4) mainly plays an anti-inflammatory role and promotes inflammation resolution. LXA4 plays an inhibiting inflammatory role in a variety of diseases, tissues and cells, including keratinocytes. Psoriasis is a chronic inflammatory skin disease mediated by dysregulation of inflammation of immune cells and keratinocytes. However, the expression and role of LXA4 in psoriasis-like mouse models are still unclear.Methods: Imiquimod (IMQ) topical treatment of dorsal skin induces psoriasis-like dermatitis in BALB/c mice, pretreated intraperitoneally with or without LXA4 prior to IMQ application. Severity of dorsal lesions is assessed by using a modified human scoring system and histopathology. The concentration of LXA4 and the expression of ALOX15 (a key gene in LXA4 metabolic synthesis) in lesional skins were detected by ELISA and Western blot. Quantitative PCR and ELISA were conducted to detect the mRNA and secretion levels of inflammatory cytokines. The proportion of IL-17A-producing γδT cells in skin and skin draining cervical lymph nodes and helper (Th) 17 cells in spleens was evaluated by flow cytometry. Western blotting was used to analyze the expressions of p-STAT3 and TRAF6.Results: The concentration of LXA4 and the expression of ALOX15 were decreased in IMQ-induced lesional skin. LXA4 significantly relieved psoriasis-like lesions in IMQ-induced mouse models. Furthermore, LXA4 decreased IMQ-induced systemic inflammation, including reduced the proportion of IL-17A-producing gdT cells in skin and skin draining cervical lymph nodes and Th17 cells in spleens, the secretion and expression of CCL20, IL-17A, IL-1β, and TNF-α in skin and serum. LXA4 markedly inhibited IMQ-induced expression of TRAF6 and p-STAT3.Conclusion: LXA4 significantly ameliorates IMQ-induced psoriasis-like inflammation, and LXA4 can be used as a target for psoriasis treatment.Keywords: lipoxin A4, psoriasiform dermatitis, imiquimod, γδT cells, Th17, inflammation