title: Kinetics of chemokines and their receptors in mercuric chloride-induced tubulointerstitial lesions in brown Norway rats.
abstract: We investigated the kinetics of chemokines and their receptors in mercuric chloride-treated brown Norway (BN) rats from the viewpoint of its relation to the development of tubulointerstitial fibrosis with mononuclear cell infiltration. BN rats were injected subcutaneously with 1 mg/kg b.w. of mercuric chloride one or three times. The kidney was examined histopathologically and the kinetics of chemokines and their receptors in the kidney were also examined using immunohistochemistry and RT-PCR. As a result, mercuric chloride induced tubular injury and subsequent tubulointerstitial fibrosis accompanied with mononuclear cell infiltration. Macrophages were the most predominant population of infiltrating cells and lymphocytes were the next. In the lesions, the expression of MCP-1 mRNA was most prominently elevated, and those of RANTES and IP-10 mRNAs also increased, and their proteins were localized in tubular epithelium. As to their receptors, the levels of CCR1, CCR2, and CXCR3 mRNAs showed significant and prominent elevations, CCR5 mRNA also increased moderately, and their receptor protein-expressing cells also increased. The present findings suggest that MCP-1, RANTES, and IP-10 may participate in the pathogenesis of mercuric chloride-induced tubulointerstitial fibrosis with mononuclear cell infiltration, via CCR2, CCR1 or CCR5, and CXCR3, respectively.
authors.affiliation: Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan. akunio@mail.ecc.u-tokyo.ac.jp
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Suzuki
authors.forename: Tomomichi
authors.initials: T
authors.lastname: Kanabayashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakayama
authors.forename: Kunio
authors.initials: K
authors.lastname: Doi
mesh_terms: D000818:Animals; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D004202:Disinfectants / Q000633:toxicity; D005355:Fibrosis / Q000473:pathology*; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D007684:Kidney Tubules / Q000276:immunology* / Q000473:pathology; D007700:Kinetics; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity; D009395:Nephritis, Interstitial / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011914:Rats, Inbred BN; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D018925:Chemokines; D017931:DNA Primers; D004202:Disinfectants; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D008627:Mercuric Chloride