Activation of the HMGB1-TLR4-NF-κB pathway may occur in patients with atopic eczema

High mobility group protein B1 (HMGB1) has been reported to serve important roles in various pathological conditions. Toll-like receptor 4 (TLR4), as one of the HMGB1 receptors, has been reported to be involved in the development of certain inflammatory diseases by activating nuclear factor NF-κ-B (NF-κB). However, there are few studies investigating the effects of HMGB1, TLR4 and NF-κB on human inflammatory dermatoses. In the present study, the distribution and characteristics of HMGB1, TLR4 and NF-κB p65 expression in psoriasis and atopic eczema (AE) were investigated. In addition, immunohistochemical analysis was performed to evaluate their expression and distribution in normal skin, and in patients with AE or psoriasis. Spearman's correlation analysis was used to predicate their relevancy. The present study identified that the p65 level in epithelial nuclei in AE skin was increased compared with normal and psoriasis skin (P<0.01). The level of extracellular HMGB1 in AE skin was also increased compared with normal and psoriasis skin (P<0.01). Meanwhile, TLR4 expression on the epithelial membranes of AE skin was increased compared with psoriasis skin (P<0.01). Furthermore, the level of extracellular HMGB1 was positively correlated with epithelial membrane TLR4 (r=0.3856; P<0.05) and epithelial nuclear p65 (r=0.5894; P<0.01) in AE skin. These results indicated that the HMGB1-TLR4-NF-κB signaling pathway is activated in AE and may account for its pathogenesis, but not in psoriasis. Therefore, HMGB1, TLR4 and NF-κB p65 have the potential to be targets for the treatment of human inflammatory dermatoses, including AE.