Expressions Of IL-36Cytokines And Their Relationship With P38MAPK And NF-κB Pathways In Psoriasis Vulgaris Skin Lesions

Background Psoriasis, which has genetic predisposition, is a kind of common chronic inflammatory dermatosis. The population of people suffering from this disease is about2%or3%of the total, especially in Canada and America. Psoriasis has a complicated etiology involving genetic, immune, environmental factors and so on, whose pathogenesis is always the focus of recent medical study. A number of studies demonstrated that mitogen-activated protein kinase(MAPK) and nuclear factor-κB(NF-κB) pathways played crucial roles in immune procession of many chronic inflammatory diseases such as psoriasis. Although the activation mechanisms in diseases are still unclear, the two signal pathways can affect and regulate the production and release of various chemokines, inflammatory mediators and adherent cytokines and are closely related to the maintenance of inflammation. Advanced data showed that the novel member of interleukin-1(IL-1) family, interleukin-36(IL-36) played an important role in pathogenesis of psoriasis, whereas its exact affects and action are still on the study. Recent years, some research approved that IL-36receptor antagonist(IL-36Ra), accompany with IL-36a, IL-36β and IL-36γ, could make up a relatively independent signaling system enabling the activation of MAPK and NF-κB pathways and the function of them in the subsequent immune responds. Yet to date, little study has been done focusing on the correlation between IL-36cytokines and MAPK or NF-κB pathway in psoriasis.Objective To study the expressions of IL-36cytokines and their relationship with p38MAPK and NF-κB pathways in lesions of psoriasis valguris.Methods Real-time Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR), Western blotting, and immunohistochemistry were used to investigate the expressions of IL-36a, IL-36β, IL-36γ, phosphorylated p38MAPK(p-p38) and nuclear factor-κBp65(NF-κBp65) in38psoriasis vulgaris lesions and17normal skins. Student’s t test and chi-square test were performed to compare the data between the two groups. Pearson bivariate correlation test was performed to analyse the correlation among cytokines in the psoriasis group at the protein level.Results The expressions of IL-36α、IL-36β、IL-36γ、p-p38and NF-κBp65in the psoriasis group were significantly higher than that in the control group(all P<0.001). The immunohistochemical staining grades of IL-36α、IL-36β and IL-36y in the psoriasis group were much higher than that in the control group(all P<0.01). Nevertheless little deference existed among the immunohistochemical staining grades of the three cytokines in the psoriasis group(P>0.05). Significant positive correlations between IL-36cytokines and p-p38or NF-κBp65(all P<0.05), as well as between p-p38and NF-κBp65(P<0.01), were observed in the skin lesions of psoriasis.Conclusions The expressions of IL-36cytokines were prominently increased in the lesions of psoriasis vulgaris. This change was considered to be related to p38MAPK and NF-κB pathways. The three agents may coact in the development of psoriasis and the local inflammation.