5,2′‐dibromo‐2,4′,5′‐trihydroxydiphenylmethanone attenuates LPS‐induced inflammation and ROS production in EA.hy926 cells via HMBOX1 induction

Abstract

Inflammation and reactive oxygen species (ROS) are important factors in the pathogenesis of atherosclerosis (AS). 5,2′‐dibromo‐2,4′,5′‐trihydroxydiphenylmethanone (TDD), possess anti‐atherogenic properties; however, its underlying mechanism of action remains unclear. Therefore, we sought to understand the therapeutic molecular mechanism of TDD in inflammatory response and oxidative stress in EA.hy926 cells. Microarray analysis revealed that the expression of homeobox containing 1 (HMBOX1) was dramatically upregulated in TDD‐treated EA.hy926 cells. According to the gene ontology (GO) analysis of microarray data, TDD significantly influenced the response to lipopolysaccharide (LPS); it suppressed the LPS‐induced adhesion of monocytes to EA.hy926 cells. Simultaneously, TDD dose‐dependently inhibited the production or expression of IL‐6, IL‐1β, MCP‐1, TNF‐α, VCAM‐1, ICAM‐1 and E‐selectin as well as ROS in LPS‐stimulated EA.hy926 cells. HMBOX1 knockdown using RNA interference attenuated the anti‐inflammatory and anti‐oxidative effects of TDD. Furthermore, TDD inhibited LPS‐induced NF‐κB and MAPK activation in EA.hy926 cells, but this effect was abolished by HMBOX1 knockdown. Overall, these results demonstrate that TDD activates HMBOX1, which is an inducible protective mechanism that inhibits LPS‐induced inflammation and ROS production in EA.hy926 cells by the subsequent inhibition of redox‐sensitive NF‐κB and MAPK activation. Our study suggested that TDD may be a potential novel agent for treating endothelial cells dysfunction in AS.

Protective effect of surfactin on copper sulfate‐induced inflammation, oxidative stress, and hepatic injury in zebrafish

“…It has been reported that NF-κB is released into the cell nucleus and binds to genes to initiate transcription leading to inflammation, oxidative stress, and apoptosis after being stimulated by some external factors. [45][46][47] NO is synthesized by iNOS, COX-2. In terms of some metal iron induced inflammatory response, NF-κB controls the expressions of NO to reduce inflammatory reaction.…”

HMBOX1 attenuates LPS‑induced periodontal ligament stem cell injury by inhibiting CXCL10 expression through the NF‑κB signaling pathway

“…The present study found also that increased HMBOX1 inhibited NF-κB activation in hPDLSCs in response to LPS. In addition to the potential involvement of NF-κB in the regulatory role of HMBOX1 in response to LPS, a previous study also showed that 5'AMP-activated protein kinase mediates the regulation of HMBOX1, which is associated with inflammation after EA.hy926 cells were subjected to LPS stimulation (9). Additionally, HMBOX1 has been reported to be involved in cancer progression in an AKT-dependent manner, including osteosarcoma, lung cancer and liver cancer (23)(24)(25).…”

“…In addition, the NF-κB signaling pathway was found to upregulate the expression of CXCL10 in COMM domain-containing protein 7-treated hepatocellular carcinoma cells (18). Aldo-keto reductase family 1 member C2 was also discovered to exert potent anti-inflammatory and antioxidant effects by inhibiting NF-κB activity downstream of HMBOX1 activation in an atherosclerosis model of LPS-induced EA.hy926 cells (9).…”

“…Homeobox containing 1 (HMBOX1) is a member of the homeobox transcription factor family that has been identified to serve a role in a large number of biological processes including proliferation, inflammation and apoptosis (7)(8)(9)(10). A previous genomic and proteomic analysis found that the expression levels of HMBOX1 were downregulated in gingival tissues from patients with periodontitis compared with a control group without periodontitis, which identified a potential association between HMBOX1 expression levels and the pathogenesis of periodontitis (11).…”

Perspectives in the Cell-Based Therapies of Various Aspects of the Spinal Cord Injury-Associated Pathologies: Lessons from the Animal Models

“…On the other hand, overexpression of miRNA-124 in MSCs was shown to drive their differentiation into neurons and promote functional recovery of spinal rats [ 92 ]. However, another possible mechanism for this recovery could be the decrease in the number of apoptotic cells; miRNA-124 blocks the mitochondrial pathway of apoptosis in vivo [ 93 ] and LPS-induced apoptosis in vitro [ 94 ].…”