Endoplasmic Reticulum Stress in Glomerulonephritis

Abstract

The balance between somatic cellular machinery for defense against local effector molecules determines the tissue fate of inflammation—progression or resolution. We previously proposed the concept of glomerular “self-defense” as essential for spontaneous subsidence of glomerular inflammation.1 A line of evidence supporting this concept is that glomeruli, when faced with activated leukocytes or exposure to pathogenic factors, defend themselves through intrinsic machinery brought into play in resident glomerular cells. For example, in glomeruli isolated from the regeneration phase of anti-Thy 1 GN, induction of inflammatory genes is blunted in vitro .1–3 When activated macrophages are adoptively transferred into the nephritic glomeruli, ex vivo induction of chemokines is also suppressed compared with the induction produced by normal glomeruli.2,3 Kawachi et al. also provides in vivo evidence. In an acute model of anti-Thy 1 GN, macrophages accumulate within 24 h and peak at 1 wk. However, when Thy 1 inflammation is reinduced 2 wk after the first administration of anti-Thy 1 antibody, accumulation of macrophages is suppressed.4 These results indicate the possibility that, once activated, glomerular cells acquire a tolerance against subsequent exposure to inflammatory stimuli. Under inflammatory conditions, various molecules are induced by activation of NF-κB, something …