Spatiotemporal spread of inflammation caused by HMGB1 nuclear DNA-binding protein

2012 Fiscal Year Final Research Report

• Project/Area Number: 23790447
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Kagoshima University
• Principal Investigator: OYAMA Yoko 鹿児島大学, 医学部・歯学部附属病院, 特任助教 (20583470)
• Project Period (FY): 2011 – 2012
• Keywords: High mobility group box-1 protein / RAGE / TLR2 / TLR4 / Thrombomodulin / Reactive oxygen species

Research Abstract

High-mobility group box-1 protein (HMGB1) was originally described as a nuclear DNA-binding protein that facilitates gene transcription by stabilizing nucleosome formation. HMGB1 can also be released or secrete extracellularly from cells as a result of cellular necrosis or activated macrophages/monocytes in response to inflammatory stimuli respectively, and acts as a pro-inflammatory cytokine or alarm signal for tissue damage. We have revealed that HMGB1 can trigger a potent inflammatory response and accelerates granulomatous inflammation leading to severe tissue injury. In this study, we tried to disclose further mechanism of HMGB1- associated granulomatous inflammation. From a point of view that controlling HMGB1 is essential for treatment of granulomatous nephritis, we studied experiments using a granulomatous nephritis animal model to investigate follows;
1． The relationship between degrees of the nephritis and HMGB1 receptors expression
2． The effect of anti-HMGB1 antibody
3． TM association of the nephritis
4． Reactive oxygen species association of the nephritis
We have found that receptors of HMGB1 and TM could be a target for inhibiting granulomatous nephritis.