IL-33 Antibody Alleviates Imiquimod-induced Psoriasis-like Dermatitis In Mice

BackgroundPsoriasis is a chronic inflammatory skin disease.The clinical presentation is based on typical erythematous and scaly skin lesions.Interleukin-33,a new member of the interleukin-1 cytokine family,is constitutively expressed in the epithelial cells of the skin.IL-33 enhanced mast cells and neutrophils and collect the evidence to promote inflammation.IL-33 promote angiogenesis,inflammation,in turn,stimulates the immune cells raised parts,which has a significant role in psoriasis.Our previous study showed that interleukin-33 contributed to the severity of the disease in psoriasis-like mouse models.The research checked whether the IL-33 antibody inhibited psoriasis-like inflammation using an IMQ-induced model in mice.ObjectiveThese results indicate the therapeutic effect of IL-33 antibody against IMQ-induced psoriatic dermatitis model in mice and its possible anti-inflammatory mechanisms.MethodsBefore the treatment,the back skin of the BALB/c mice was depilated utilizing an electric clipper.A daily topical dose of 5%IMQ cream or vaseline cream on the back was applied.The mice were randomly divided into five groups（n=6 per group）:（1）Control group,（2）IMQ group;（3）IMQ+Ig G group（IMQ plus Ig G）;（4）IMQ+IL-33 antibody group（IMQ plus IL-33 antibody）and（5）IMQ+PBS group（IMQ plus PBS）.In this study,IL-33 antibody/Ig G was dissolved in PBS and injected by subcutaneous injection（i.h）.The mice in the IMQ group were treated with 62.5 mg of 5%IMQ cream once a day for six consecutive days（days 0-5）.100μl（1μg/100μl）IL-33 antibody or100μl（1μg/100μl）Ig G/PBS was injected into the subcutaneous injection of the mice every day from the first day to day six.Western blot was used to detect the protein expression levels of STAT3,p-STAT3 and IL-33 in the back skin of mice in each group;Real-time Quantitative PCR was used to detect the expression of IL-33,ST2,IL-1,IL-6,IL-10 and TNF-α;HE staining was used to observe the proliferation of mice in each group;Immunohistochemical analysis of the expression of proliferating cell-related antigen Ki-67;Immunofluorescence detection of the expression of lymphocyte surface antigens such as CD3⁺CD8⁺T and CD3⁺CD4⁺T.Results1.IL-33 antibody efficiently decreased the erythema（P<0.05）,scaling（P<0.05）and average epidermal thickness（P<0.001）compared with the IMQ group,in addition,the spleen index also decreased（P<0.01）.2.Contrasted with the IMQ group,p-STAT3（P<0.001）levels protein and IL-33（P<0.001）protein levels in mice from the IL-33 antibody group were significantly decreased,while STAT3 protein levels was increased（P<0.001）..3.Compared to the IMQ group,the results demonstrated that the expression of inflammatory cytokines in the skin were all dramatically decreased after IL-33 antibody treatment,while IL-10 levels expression was increased（P<0.01）.4.Analysis of IHC showed markedly reduced Ki-67 in the epidermis of IL-33antibody mice compared with those treated with IMQ alone.5.IL-33 antibody markedly reduced the infiltration of CD3⁺CD4⁺T cells and CD3⁺CD8⁺T cells in the dermis compared with the IMQ group.ConclusionThe research showed that the IL-33 antibody alleviated the seriousness of skin lesions in imiquimod-induced psoriasiform dermatitis in mice by inhibiting the activation of the STAT3 signal pathway and lymphocyte infiltration and the secretion of pro-inflammatory cytokines suggesting IL-33 antibody poses a potentially significant therapeutic benefit to psoriasis.