Role of macrophage migration inhibitory factor in bleomycin-induced lung injury and fibrosis in mice.
Macrophage migration inhibitory factor (MIF) is a unique cytokine that reportedly overrides the anti-inflammatory effect of endogenous glucocorticoids. MIF has been demonstrated to be involved in a variety of inflammatory diseases. In this study, we examined the role of MIF in bleomycin (BLM)-induced lung injury and fibrosis. The levels of MIF in lung tissues and bronchoalveolar lavage fluids were significantly increased in the period 5-10 days after intratracheal administration of BLM. Treatment with the anti-MIF antibody significantly reduced the mortality at 14 days and the histopathological lung injury score at 10 days. These effects were accompanied with significant suppression of the accumulation of inflammatory cells in the alveolar space and tumor necrosis factor-alpha in the lungs at 7 days. However, the anti-MIF antibody did not affect either the content of lung hydroxyproline or the histopathological lung fibrosis score at 21 days after BLM. These data provide further evidence for the crucial role of MIF in acute lung inflammation but do not support the involvement of MIF in lung fibrosis induced by BLM in mice.
Tanino
Yoshinori
Y
First Department of Medicine, Hokkaido University School of Medicine, Sapporo 060-8638, Japan. ytanino@med.hokudai.ac.jp
Makita
Hironi
H
Miyamoto
Kenji
K
Betsuyaku
Tomoko
T
Ohtsuka
Yoshinori
Y
Nishihira
Jun
J
Nishimura
Masaharu
M
D000818:Animals; D000903:Antibiotics, Antineoplastic; D000906:Antibodies / Q000494:pharmacology; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D018932:Chemokine CCL2 / Q000032:analysis; D054426:Chemokine CXCL2; D018925:Chemokines / Q000032:analysis; D009075:MSH Release-Inhibiting Hormone / Q000032:analysis / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011650:Pulmonary Alveoli / Q000737:chemistry / Q000276:immunology* / Q000473:pathology*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000401:mortality / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000903:Antibiotics, Antineoplastic; D000906:Antibodies; D018932:Chemokine CCL2; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin; D009075:MSH Release-Inhibiting Hormone