HMGB1 Increases IL-1β Production in Vascular Smooth Muscle Cells via NLRP3 Inflammasome

• DOI: 10.3389/fphys.2018.00313
• Publication Date: 2018-03-28T04:26:31Z
• Authors: Eun Jung Kim; So Youn Park; Seung Eun Baek; Min A. Jang; Won Suk Lee; Sun Sik Bae; Koanhoi Kim; Chi Dae Kim
• Keywords: HMGB1; Proinflammatory cytokine; RAGE; Pyroptosis; TRIF

Vascular smooth muscle cells (VSMCs) are the major cell type in blood vessel walls, and their phenotypic modulation is a key cellular event driving vascular remodeling. Although high mobility group box-1 (HMGB1) plays pivotal role inflammatory processes after injuries, importance of links between VSMCs, HMGB1 inflammation has not been clarified. To prove hypothesis that VSMCs might be active players by secreting cytokines, we investigated proinflammatory effects its intermediary signaling pathways VSMCs. When cultured human were stimulated with (10 to 500 ng/ml), IL-1β production was markedly increased. also increased expression NLRP3 inflammasome components including NLRP3, ASC caspase-1. Among these components, HMGB1-induced expressions caspase-1 attenuated TLR-2 siRNA-transfected cells, whereas reduced RAGE-deficient cells. In TLR4-deficient significantly attenuated. Moreover, HMGB1-stimulated transfected siRNA as well treated monoclonal antibodies or siRNAs for TLR2, TLR4 RAGE. Overall, this study identified receptor involved HMGB1. Thus, targeting offers promising therapeutic strategy treating remodeling diseases.