Involvement of leukotrienes in the pathogenesis of silica-induced pulmonary fibrosis in mice.
The authors investigated the role of leukotrienes (LTs) in the pathogenesis of silica-induced pulmonary fibrosis in mice during the progression from acute to chronic phases. Intratracheal instillation of silica particles induced progressive pulmonary fibrosis. The tissue content of cysteinyl (Cys) LTs and LTB(4) was markedly increased in the acute phase after silica instillation, concurrently with the up-regulation of LTB(4) receptor, transforming growth factor (TGF)-beta1, and tumor necrosis factor (TNF)-alpha, along with down-regulation of the CysLT type 2 receptor. Importantly, the tissue content of CysLTs and mRNA levels of TGF-beta1 and TNF-alpha were increased in the fibrotic lung in the chronic phase. Furthermore, strong immunohistochemical staining for the CysLT type 1 receptor, TNF-alpha, and TGF-beta1, but not for the CysLT type 2 receptor, was codetected in the pathological lesions during both acute and chronic phases. These findings suggest that an increase in LT production in the lung and modulation of homeostatic balance among LT receptors may contribute to the progression of pulmonary fibrosis.
Shimbori
Chiko
C
Department of Pharmacology, Shimane University School of Medicine, Izumo, Shimane, Japan.
Shiota
Naotaka
N
Okunishi
Hideki
H
D000208:Acute Disease; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D003545:Cysteine / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006909:Hydroxyproline / Q000378:metabolism; D007150:Immunohistochemistry; D007975:Leukotriene B4 / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism*; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D018077:Receptors, Leukotriene / Q000378:metabolism; D018102:Receptors, Leukotriene B4 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012822:Silicon Dioxide; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D015289:Leukotrienes; C503704:Ltb4r1 protein, mouse; D012333:RNA, Messenger; D018077:Receptors, Leukotriene; D018102:Receptors, Leukotriene B4; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C112381:cysteinyl-leukotriene; D007975:Leukotriene B4; D012822:Silicon Dioxide; C412375:cysteinyl leukotriene receptor 2; D003545:Cysteine; C083169:leukotriene D4 receptor; D006909:Hydroxyproline