Hayakawa, K.Hiramatsu, N.Okamura, M.Yao, J.Paton, A.Paton, J.Kitamura, M.2009-09-042009-09-042008Biochemical and Biophysical Research Communications, 2008; 365(1):47-530006-291X1090-2104http://hdl.handle.net/2440/50752Copyright © 2008 Elsevier Inc. All rights reserved.Geranylgeranylacetone (GGA), an anti-ulcer agent, has anti-inflammatory potential against experimental colitis and ischemia-induced renal inflammation. However, molecular mechanisms involved in its anti-inflammatory effects are largely unknown. We found that, in glomerular mesangial cells, GGA blocked activation of nuclear factor-κB and consequent induction of monocyte chemoattractant protein 1 (MCP-1) by inflammatory cytokines. It was inversely correlated with induction of unfolded protein response (UPR) evidenced by expression of 78 kDa glucose-regulated protein (GRP78) and suppression of endoplasmic reticulum stress-responsive alkaline phosphatase. Various inducers of UPR including tunicamycin, thapsigargin, A23187, 2-deoxyglucose, dithiothreitol, and AB5 subtilase cytotoxin reproduced the suppressive effects of GGA. Furthermore, attenuation of UPR by stable transfection with GRP78 diminished the anti-inflammatory effects of GGA. These results disclosed a novel, UPR-dependent mechanism underlying the anti-inflammatory potential of GGA.enGeranylgeranylacetoneMesangial cellTumor necrosis factor-αUnfolded protein responseEndoplasmic reticulum stressMonocyte chemoattractant protein 1Nuclear factor-κBJournal article002008000810.1016/j.bbrc.2007.10.1150002514939000082-s2.0-3604899341743959Paton, J. [0000-0001-9807-5278]