2001 Fiscal Year Final Research Report Summary
Treatment of acute lung injury by inhibition of gene induction of NO synthase in alveolar macrophages.
| Project/Area Number |
12670579
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Tokyo Woman's Medical University |
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Principal Investigator |
TAMAOKI Jun Tokyo Women's Medical University Depertment of Medicine, Assc Prof., 医学部, 助教授 (60147395)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Macrophage / Nitric Oxide / Gene therapy / Lung injury / Cytokines / Macrolide / Erythromycin / Clarithromycin |
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| Research Abstract |
Macrolide antibiotics have unique immunomodulatory actions apart from antimicrobial properties. We studied the effects of macrolides on immunoglobulin G immune complex (IgG-ICx)-induced lung injury in rats in vivo and in vitro. Intrapulmonary deposition of IgG-ICx produced a time-dependent increase in the concentration of NO in exhaled air. There were corresponding increases in the number of neutrophils accumulated into alveolar spaces, and lung wet-to-dry weight ratio. All of these changes were inhibited by pretreatment with erythromycin or josamycin, but not by amoxicillin or cephaclor. Incubation of cultured pulmonary alveolar macrophages (PAM) caused upregulation of NO production and expression of inducible NO synthase (iNOS) mRNA, an effect that was dose dependently inhibited by erythromycin, roxithromycin, or josamycin. The macrolides also reduced IgG-ICx-induced release of IL-1* and TNF-α, but did not alter the release of NO induced by exogenously added IL-1β and TNF-α. These results suggest that macrolide antibiotics specifically inhibit immune complex-induced lung injury presumably by inhibiting cytokine release and the resultant downregulation of iNOS gene expression and NO production by rat PAM.
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