Effects of tacrolimus and dexamethasone on tubulointerstitial fibrosis in mercuric chloride treated Brown Norway rats.
We investigated the effects of daily injection of tacrolimus (FK), an immunosuppressor, or dexamethasone (Dx), an antiinflammatory agent, on renal tubulointerstitial fibrosis in mercuric chloride-treated Brown Norway rats. The tubular lesions observed after one time injection of mercuric chloride were reduced in FK-treatment group, but not in Dx-treatment group. Moreover, FK reduced infiltration of mononuclear cells, especially macrophages, and proliferation of myofibroblasts in renal intestitium and also inhibited renal interstitial fibrosis through the reduction of the expressions of fibrosis-related factors, i.e. plasminogen activator inhibitor-1 and transforming growth factor-beta1. On the other hand, Dx reduced lymphocyte infiltraton, but did not inhibit macrophage infiltration. In addition, Dx did not suppress myofibroblast profiferation, upregulation of fibrosis-related factors, and interstitial fibrosis. From these findings, it is suggested that FK may inhibit renal interstitial fibrosis through inhibition of macrophage infiltration, and that macrophages and myofibroblasts are very important fibrogenic factors in the development of mercuric chloride-induced renal tubulointerstitial fibrosis in BN rats.
Suzuki
Kazuhiko
K
Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
Kanabayashi
Tomomichi
T
Nakayama
Hiroyuki
H
Doi
Kunio
K
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005347:Fibroblasts / Q000187:drug effects; D005355:Fibrosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D009395:Nephritis, Interstitial / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D008627:Mercuric Chloride; D003907:Dexamethasone; D016559:Tacrolimus