Relevant Study Between Pathogenesis Of Psoriasis Vulgaris And IL36,IL36Ra,IL38 Cytokines

Background and Objective: Psoriasis is a chronic erythema scaly dermatosis,which is mediated by dysimmunity driven by multiple genes and follows multiple steps.The complicate pathogenesis of psoriasis brings huge problems for psoriatic treatment and intervention.Studies in recent years have suggested that cytokines have an impact on the process of the generatiion and development of psoriasis.The lesion and peripheral blood circulation of patients with psoriasis may produce a variety of cytokines.The activation of pro-inflammatory cytokines can induce and aggravate inflammation.Anti-inflammatory cytokinesmay inhibit inflammation through blocking the production and releasingof pro-inflammatory cytokines,orthrough competitive inhibition of pro-inflammatory medias.Therefore,the inflammatory imbalance plays a significant role in the process of psoriasis.Interleukins 36 is a important member of IL-1 family.It has sub-family members,including IL-36??IL-36??IL-36? and a receptor antagonist named IL-36 Ra.Activated keratinocytes,monocytes and B cells can produce IL-36.Once different kinds of IL-36 bind with the receptor IL-36 R,the signal cascade of MAPKs/JNK/ERK will be activated,then starting the expression of two nuclear transcriptions factors,NF-k B and AP-1,initiate the expression of target genes,in order to exert pro-inflammatory.effects.As a receptor antagonist of IL-36,IL-36 Ra exerts thecompetitive inhibitioneffect through binding with IL-36 R.Researches found that IL-38 has a similar function to IL-36 Ra.It can also bind with IL-36 R to inhibit the production of IL-17 and IL-22 by Th17 cells,whichis definitely involved in the pathogenesis of psoriasis.IL-36,IL-36 Ra and IL-38 have built a specific signal system,however,it is still not clear how the system works,how the proportion of IL-36/IL-36 Ra and IL-36/IL-38 changes,and whether the inflammatory imbalance is involved in the whole inflammatory process of psoriasis.In the present study,we aim to preliminarilydiscuss the role of IL-36,IL-36 Ra and IL-38 in the pathogenesis of psoriasis vulgaris(PV).Materials and Methods: 1.Study on the expression of IL-36,IL-36 Ra and IL-38 in the skin tissue of patients with psoriasis vulgaris 34 PV patients were recruited,20 normal skin specimens from healthy people were also selected as the control group.Immunhistochemical staining(IHC)was applied to detect the expression of IL-36,IL-36 Ra and IL-38 in the skin tissue of the case and the control group.Alltissues were observed under a microscope and photograph through slicing,dewaxing,adding antibody,incubation,coloring,dehydration and sealing.The Image-Pro Plus 6.0 analysis system was applied to measure the integrated optical density of IL-36,IL-36 Ra and IL-38.The average optical density was calculated to reflect the expression of target proteins.2.Study on the expression levels of IL-36,IL-36 Ra and IL-38 in the peripheral blood and their correlations with PASI score in psoriasis vulgaris.29 PV patients were selected,19 healthy controlswere also selected.All patients were assessed by PASI.We collected and separated the peripheral blood of all the subjects,then ELISA was used to measure the expression levels of IL-36,IL-36 Ra and IL-38.The difference of the plasmic expression of IL-36,IL-36 Ra and IL-38 between the cases and the healthy controlswas assessed bythe rank test(Mann-Whitney U)for quantitative datas.The correlations between the expression levels of IL-36,IL-36 Ra and IL-38 and PASI scoreswere analyzed by the spearman rank correlation test.Result: 1.We did not find different expression of IL-36? between thecases and control group.In PV group,IL-36? widely distributed in endochylema,nuclei and around the nucleus.There was only a small quantity of expression in stratum spinosum in control group.In PV group,IL-36? mainly distributed in granular layer and top half of stratum spinosum,while in control group,IL-36? expressed little or did not express.IL-36 Ra almost did not express in PV group,but mainly distributed at basal layer and lower part of stratum spinosum in control group.IL-38 distributed at the endochylema of epidermal layer in PV group,but only expressed at the endochylema of stratum spinosum in the healthy controls.2.The average optical density of IL-36? between psoriasis patients and healthy controls has no statistical difference(P>0.05).The average optical density of IL-36? and IL-36?significantly increased in psoriasis vulgaris(P<0.01).The average optical density of IL-36 Ra and IL-38 in psoriasis vulgaris were lower than those in healthy controls(P<0.01).3.Compared with the healthy controls,the expression levels of IL-36??IL-36??IL-36? and IL-36 Ra in peripheral blood increased(P<0.01),while the expression level of IL-38 significantly decreased(P<0.01)4.There were positive correlations between the plasmic expression of IL-36?,IL-36? and PASI score(P < 0.01).The plasmic expression of IL-38 was negatively correlatedwith PASI score(P<0.01).There were no correlation between the expression of IL-36? and IL-36 Ra and the PASI score.Conclusions: 1.The expression of pro-inflammatory factors,IL-36? and IL-36 ?,increased in the lesion of psoriasis vulgaris,which indicated that the activation of IL-36? and IL-36 ? was involved in the pathogenesis of psoriasis.The significant reduction of the expression of IL-36 Ra and IL-38 in the lesion of psoriasis vulgaris suggested that subdued antagonism of anti-inflammatory factors may have an impact on the occurrence and development of psoriasis.2.Prominent up-regulation of the plasmic expression of IL-36?,IL-36? and IL-36? in psoriasis vulgaris demonstrated that pro-inflammatory factor IL-36 may play a vital role in the pathogenesis of psoriasis.The difference of the expression of IL-36 Ra in skin tissue and plasma indicated that pro-inflammatory molecules in skin tissue and circulation system may have different functionpatterns.Down-regulation of IL-38 expression in plasma further suggests that the imbalance between pro-inflammatory molecules and anti-inflammatory factors participated in the pathogenesis of psoriasis.3.The levels of IL-36? and IL-36? in the plasma were positively correlated with PASI score,while IL-38 was negatively correlated with PASI score,which suggested that the plasma levels of these factors may be served as important markers in evaluation of the severity of psoriasis vulgaris.The present study also provided a new target and theoretical basis for the clinical treatment of psoriasis.