Relationship of heat shock protein 25 with reactive macrophages in thioacetamide-induced rat liver injury.
Heat shock protein 25 (Hsp25), which has anti-inflammatory activity, was examined for the relationship of its expression to macrophage appearance in thioacetoamide (TAA)-induced rat acute hepatic lesions. TAA-induced lesions, consisting of hepatocyte coagulation necrosis and reactive macrophages, developed in the centrilobular areas. Macrophages immuno-reacting to ED1 (CD68; exudative macrophages) were mainly seen within the lesions, whereas macrophages reacting to ED2 (CD163; resident macrophages and Kupffer cells), which have abundant cytoplasm, appeared mainly in the periphery of the lesions. Hsp25-immunopositivity was seen in hepatocytes around the lesions in relation to ED1- and ED2-positive macrophages in and around the centrilobular lesions, respectively. Because macrophages appearing in early stages of hepatic lesions produce various pro-inflammatory factors, mRNA expressions of tumor necrosis factor-α (TNF-α), monocyte chemoattractant factor-1 (MCP-1) and osteopontin (OPN) were examined in relation to Hsp25 mRNA expression. Hsp25 mRNA expression generally was correlated with TNF-α, MCP-1 and OPN expressions, suggesting their direct or indirect association with Hsp25 expression. Thus, Hsp25 might have a cytoprotection function against macrophages appearing in hepatic lesions, and factors produced by macrophages in the very early stages of hepatic lesions may influence Hsp25 expression. Hsp25 expression should be useful as an index of anti-inflammatory action for evaluation of hepatotoxicants in vivo.
Fujisawa
Kae
K
Developmental Research Laboratories, Shionogi & Co., Ltd, 3-1-1, Futaba-cho, Toyonaka, Osaka 561-0825, Japan. kae.fujisawa@shionogi.co.jp
Miyoshi
Takako
T
Tonomura
Yutaka
Y
Izawa
Takeshi
T
Kuwamura
Mitsuru
M
Torii
Mikinori
M
Yamate
Jyoji
J
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018932:Chemokine CCL2 / Q000096:biosynthesis; D004195:Disease Models, Animal; D055551:HSP27 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D022781:Hepatocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008111:Liver Function Tests; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D053495:Osteopontin / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013853:Thioacetamide / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D055551:HSP27 Heat-Shock Proteins; C486114:Hspb1 protein, rat; D012333:RNA, Messenger; C506897:Spp1 protein, rat; D014409:Tumor Necrosis Factor-alpha; D013853:Thioacetamide; D053495:Osteopontin