643 Heat stimuli induces beige adipocytes differentiation and browning of the subcutaneous fat tissues in human skin

Abstract

High mobility group box 1" (HMGB1) is a well-known nuclear protein that stabilizes DNA and facilitates gene transcription, but at outside the membrane, it functions as an alarmin, causing an inflammatory response in combination with other cytokines. Recently, we confirmed that HMGB1 shows the proinflammatory activity depending on the redox status, which is in the reduced, disulfide, or oxidized form. The reduced-HMGB1 exerts a chemoattractive effect, and the disulfide-HMGB1 has proinflammatory cytokine activity, but the oxidized form has no inflammatory activity. In our previous study, the proinflammatory effect of disulfide-HMGB1 was seen under the poly(I:C)-induced inflammation in keratinocyte, but reduced-HMGB1 showed the suppressive effect of poly(I:C)-induced inflammation. In addition, HMGB1 contains two homologous DNA-binding domains, the A and B-boxes. HMGB1 B-box induces strong proinflammatory activities, but HMGB1 A-box is a specific antagonist for HMGB1 and exerts an anti-inflammatory effect in macrophage. However, the direct effects of HMGB1 A-box and B-box for keratinocytes were not well elucidated. To investigate those effects, we established recombinant peptides for HMGB1 A-box and B-box. HMGB1 A and B-box alone did not induce inflammatory cytokines for keratinocyte on own. On the other hand, HMGB1 A-box had suppressive effect for IL-6 and IFN-beta expression on poly (I:C) induced inflammation in keratinocyte, but HMGB1 B-box had no inflammatory in keratinocytes. From these results, it is possible that HMGB1 A-box could become a new antiinflammatory material for some inflammatory skin diseases.