The Role Of HMGB1 In The Pathogenesis Of Lichen Planus

Bakground:Lichen planus(LP)is a chronic inflammatory skin disease of unknown cause.Recent studies has demonstrated a variety of inflammatory mediators are involved in the pathogenesis.As a representative molecules of damage associated molecular patterns High mobility group box-1(HMGB1)has been implicated as a pro-inflammatory cytokine in the pathogenesis of various inflammatory and autoimmune diseases.However,mechanism of HMGB1 in lichen planusis still unknown.Objective:Detecting the expression of HMGB1 in LP and normal skin,explore the role of HMGB1 in pathogenesis of lichen planus.Methods:Immunohistochemical SP was used to detect the expression of HMGB1 in lesion of lichen planus and normal skin,then compared the expression of HMGB1 in different subtypes of lichen planus,different region of lichen planus,different phase and Correlation analyses between percentage of HMGB1+ nuclei in epidermal cells and the amount of dermal inflammation.Result:1.The expression of HMGB1 was decreased in nuclear,but increased in cytoplasm and extracellular space of epidermal cells in lichen planus than in normal skin(P < 0.05),and the positive staining was mainly located in the middle and lower regions of the pricklecell layer and the basal cell layer,there were also no significant difference in all detected lesions and normal skin tissures.2.The expression of HMGB1 protein in different subtypes of lichen planus(acute widespread lichen planus,chronic localized lichen planus,oral lichen planus,hypertrophic lichen planus,follicular lichen planus,reverse lichen planus,lichen planus pigmentosus,atrophic lichen planus)had the common features of lichen planus.However,there were also differences: the rate of positive nuclear in the epidermis of acute generalized lichen planus was higher than that of other subtypes,and the distribution of the cytoplasm and the extracellular space of lichen planus and atrophic lichen planus were lower than that of other subtypes.3.The expression of HMGB1 protein was also different in in different phases of lichen planus(initial,mature and paracmasis): The percent of positive nuclear in epidermal cells in the lesions of lichen planus in initial was lower than that mature and paracmasis.However,The percent of positive plasma and extracellular spaces in the epidermis of the initial phase was higher than that in the mature phase,and the percent of positive plasma and extracellular space in the lichen planus of mature phase was higher than that of the paracmasis phase.The differences werestatistically significant(P < 0.05)4.The exprssion of HMGB1 protein in diferent regions of the LP skin lesions.Nuclear:Central lesion <peripheral lesion< unaffected skin,cytoplasm: peripheral lesion was higher than Central lesion and unaffected skin,extracellular space : peripheral lesion was higher than Central lesion and unaffected skin.All differences were significant(P < 0.05).5.the dermatitis infiltration was negatively correlated with the percentage of nuclear-positive of HMGB1 in epidermis(y=-25.58X+1507 R=-0.853,p<0.001),the less nuclear-positive percentage of cells in the epidermis,the more inflammatory cell infiltration in the dermis number.Conclusion:1.Compared with normal skin,reduced HMGB1 expression in nuclear was observed in lichen planus lesions,but increased expression in cytoplasm and extracellular space,which was more significant in the early period and edge lesions of lichen planus,suggesting that HMGB1 transfer from the nucleus to the cytoplasm and the extracellular space may be associated with with inflammation in dermal.2.The positive rate of HMGB1+ nucleus in keratinocytes of lichen planus epidermis were negative correlation with dermal lymphocytic infiltration,further suggesting that HMGB1 transfer from the nucleus to the cytoplasm and the extracellular space associated with lymphocytes infiltrating in dermal.