Effects Of Ursolic Acid On Imiquimod-induced Psoriasis-like Dermatitis In Mice

BackgroundPsoriasis is a clinically common inflammatory skin disease.a number of immune cells and cytokines plays an imporant role in the development and progression of psoriasis.Ursolic acid(UA),a natural pentacyclic triterpenoid carboxylic acid,It is well known that UA possess many biological functions,for example,anti-inflammation,anticancer,antidepression,inducing autophagy activities.Interleukin-33(IL-33),a newly discovered member of the IL-1 cytokine family,is presented high expression on epithelial cells.Its receptor is ST2,which primarily is expressed on T lymphocyte.Our group previous study found that IL-33 and its receptor ST2 in skin lesion specimen of psoriasis vulgaris were experssed more higher than that of normal skin tissue specimen.UA could suppress IL-33 expression in keratinocytes line HaCaT cells induced by IFN-? in vitro,whereas it is not reported whether if UA could remit skin lesion of psoriasis.ObjectiveTo estimate the effects of UA on imiquimod-induced psoriasis-like dermatitis in mice.Methods40 female BALB/c mice of clean grade were fed routinely.When we preform the expreriment,mice were randomly divided into 4 groups: control group,model group,low-dose UA group and high-dose UA group,each group had ten mice.A model of psoriasis-like dermatitis in model group and UA group mice was established by applying 5% imiquimod for a consective 6 day.The back skin lesions was observed and scored in the light of scoring standard of PASI,and the thickness of the ear was measured.On the seventh day,mice were killed through cervical dislocation method.The skin tissue specimen were taken and observed by menas of routine H&E staining and light microcope;The expression of IL-33,ST2,CD4 and CD8 in skin leison were detected with immunohistochemistry.At the same time,the spleen of each group mice were obtained to prepare single cell suspension.The percentage of CD3+CD4+ and CD3+CD8+T cells in spleen was detected by flow cytometry.ResultsThe thickness of the ear of the control group mice was 0.17±0.05 mm,whereas the thickness of the ear of the model group mice was 0.43±0.05 mm.There was prominent statistical significance between the control group and the model group(LSD-t=0.27,P=0.27<0.001).The thickness of the ear of low-dose UA group mice was 0.37±0.05 mm,there was statistical significance between low-dose UA group model and model group(LSD-t=0.67,P=0.67<0.05).However,the thickness of the ear of high-dose UA group mice was 0.27±0.05 mm.There was prominent statistical significance between high-dose UA group and model group(LSD-t =0.17,P=0.17<0.001),according to the PASI score,we observed the back skin lesion of each group of mice.Compared with the control group,thickness in ear increased and there were typical erythema and scale in the mice back skin in model group;Pathological changes of back skin lesion mainly presented with the thickening of epidermis,involving the dermis and microabscess along with parakeratosis.However,compared to model group,these symptoms,including erythema,scale and the epidermis thickness were attenuated in UA group,especially in high-dose UA group.Furthermore,compared with the control group,the expression levels of IL-33,ST2,CD4 and CD8 increased in lesion in model group.Compared with model group,the expression levels of IL-33,ST2,CD4 and CD8 decreased in lesion in UA group.There was a more significant effect in high-dose UA group.The body weight of the control group mice was 19.70±1.26 grams,weight of the spleen was 0.12±0.040 grams.Whereas,the body weight of the model group mice was 19.59±1.06 grams and the weight of the spleen was 0.32±0.070 grams.Low-dose and high-dose UA group mice were respectively 19.97±0.97 grams,19.87±1.04 grams and the spleen weight were 0.30±0.056 grams,0.28±0.087 grams respectively.There was no statistical differences between each group.The spleen index of model group was two to three times the size of control group,in terms of the spleen index.There was no difference between model group and UA group.Compared to control group,the percentage of CD3+CD4+ and CD3+CD8+ T cells was markedly decreased in spleen of model group by flow cytometry,whereas,there was no difference between model group and UA group.ConclusionsUA could possibly alleviate imiquimod-induced psoriasiform inflammation,and decrease infiltration of T lymphocyte and expression IL-33 as well as its receptor ST2.