Endogenous n-3 polyunsaturated fatty acids protect against imiquimod-induced psoriasis-like inflammation via the IL-17/IL-23 axis.
The beneficial effects of n-3 polyunsaturated fatty acids (PUFAs) on psoriasis have been reported in rats, mice and humans, but the specific mechanisms involved have not been well defined. The present study utilized the fat-1 mouse, a transgenic model that can endogenously convert n-6 FAs into n-3 PUFAs, to directly determine if the outcomes of psoriasis were correlated with n-3 PUFAs. Wild-type (WT) and fat-1 mice, which were treated daily with imiquimod (IMQ) cream or control cream on the shaved right ear and dorsal skin, were fed the same diet. The severity of inflammation of the ear and dorsal skin was scored according to the clinical Psoriasis Area and Severity Index (PASI) and epidermal hyperplasia was measured by H&E staining. The expression of inflammatory factors in the epidermis was analyzed by immunohistochemical analysis. Flow cytometry and an enzyme-linked immunosorbent assay were used to measure the differences in the content of inflammatory factors in the blood serum and to determine which of CD4+ T cells were present in the spleen between IMQ-induced fat-1 mice and WT mice. Fat-1 IMQ-induced mice exhibited significantly lower levels of inflammatory cell-like T helper 17 cells (Th17 cells) and higher levels of regulatory T cells (Treg cells) in the spleen as compared with the WT IMQ-induced mice. n-3 fatty acids stimulated Th17 cells to produce lower levels of inflammatory factors, including interleukin (IL)-17, IL-22, IL-23 and stimulated Treg cells to produce higher anti-inflammatory factors, such as Foxp3. In conclusion, the present study provides further insight into the mechanisms involved in preventing inflammation in psoriasis-like mice by n-3 PUFAs using a fat-1 transgenic mouse model.
Department of Dermatology, Southern Medical University Affiliated Guangdong Provincial No. 2 People's Hospital, Guangzhou, Guangdong, P.R. China.
Si
S
Qin
Department of Dermatology, Southern Medical University Affiliated Guangdong Provincial No. 2 People's Hospital, Guangzhou, Guangdong, P.R. China.
Ju
J
Wen
Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong, P.R. China.
Xiao-Chun
XC
Bai
Department of Orthopaedics, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, P.R. China.
Tian-Yu
TY
Chen
Department of Dermatology, Southern Medical University Affiliated Guangdong Provincial No. 2 People's Hospital, Guangzhou, Guangdong, P.R. China.
Rong-Chang
RC
Zheng
Department of Dermatology, Southern Medical University Affiliated Guangdong Provincial No. 2 People's Hospital, Guangzhou, Guangdong, P.R. China.
Gui-Bin
GB
Zhou
Department of Dermatology, Southern Medical University Affiliated Guangdong Provincial No. 2 People's Hospital, Guangzhou, Guangdong, P.R. China.
Jing
J
Ma
Department of Dermatology, Southern Medical University Affiliated Guangdong Provincial No. 2 People's Hospital, Guangzhou, Guangdong, P.R. China.
Jie-Ying
JY
Feng
Department of Pathology, Guangdong Provincial No. 2 People's Hospital, Guangzhou, Guangdong, P.R. China.
Bi-Ling
BL
Zhong
Department of Pathology, Guangdong Provincial No. 2 People's Hospital, Guangzhou, Guangdong, P.R. China.
Yi-Ming
YM
Li
D000634:Aminoquinolines / Q000009:adverse effects; D000818:Animals; D002454:Cell Differentiation; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D000077271:Imiquimod; D007249:Inflammation / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism*; D053759:Interleukin-23 / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size; D020011:Protective Agents / Q000378:metabolism / Q000494:pharmacology; D011565:Psoriasis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism
D000634:Aminoquinolines; D016207:Cytokines; D015525:Fatty Acids, Omega-3; D018836:Inflammation Mediators; D020381:Interleukin-17; D053759:Interleukin-23; D020011:Protective Agents; D000077271:Imiquimod