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Overexpression of nitric oxide synthase by the endothelium attenuates bleomycin-induced lung fibrosis and impairs MMP-9/TIMP-1 balance.
Respirology. 2006 Sep; 11(5):546-56.R

Abstract

BACKGROUND

Nitric oxide (NO) produced by endothelial NO synthase (eNOS) is thought to effect an anti-inflammatory response, but its mechanism is still unknown.

METHODS

eNOS transgenic (eNOS-TG) mice and their littermate controls (C57/BL6) were used to clarify the role of NO derived from eNOS. Bleomycin hydrochloride (1 U/body/day) or PBS was injected intraperitoneally.

RESULTS

Subpleural fibrotic changes and hydroxyproline content in the eNOS-TG mice were significantly reduced compared with those of the wild-type (WT) mice by day 56. Administration of N(omega)-nitro-L-arginine methyl ester, a potent inhibitor of NO synthase, worsened the fibrotic response in bleomycin-treated eNOS-TG mice. Gelatinolytic activity in lung homogenates, corresponding to metalloproteinase-9 (MMP-9), was significantly increased in bleomycin-injured WT mice on day 14. In contrast, the level of tissue inhibitor of metalloproteinases-1 (TIMP-1), an endogenous MMP-9 inhibitor, was increased in the bleomycin-treated eNOS-TG mice compared with WT. Immunohistochemical analysis demonstrated that MMP-9 and TIMP-1 were strongly expressed in inflammatory cells, including subpleural fibrotic lesions.

CONCLUSION

These data suggested that eNOS overexpression attenuates bleomycin-induced lung injury by ameliorating the MMP-9/TIMP-1 balance.

Authors+Show Affiliations

Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16916326

Citation

Yoshimura, Sho, et al. "Overexpression of Nitric Oxide Synthase By the Endothelium Attenuates Bleomycin-induced Lung Fibrosis and Impairs MMP-9/TIMP-1 Balance." Respirology (Carlton, Vic.), vol. 11, no. 5, 2006, pp. 546-56.
Yoshimura S, Nishimura Y, Nishiuma T, et al. Overexpression of nitric oxide synthase by the endothelium attenuates bleomycin-induced lung fibrosis and impairs MMP-9/TIMP-1 balance. Respirology. 2006;11(5):546-56.
Yoshimura, S., Nishimura, Y., Nishiuma, T., Yamashita, T., Kobayashi, K., & Yokoyama, M. (2006). Overexpression of nitric oxide synthase by the endothelium attenuates bleomycin-induced lung fibrosis and impairs MMP-9/TIMP-1 balance. Respirology (Carlton, Vic.), 11(5), 546-56.
Yoshimura S, et al. Overexpression of Nitric Oxide Synthase By the Endothelium Attenuates Bleomycin-induced Lung Fibrosis and Impairs MMP-9/TIMP-1 Balance. Respirology. 2006;11(5):546-56. PubMed PMID: 16916326.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Overexpression of nitric oxide synthase by the endothelium attenuates bleomycin-induced lung fibrosis and impairs MMP-9/TIMP-1 balance. AU - Yoshimura,Sho, AU - Nishimura,Yoshihiro, AU - Nishiuma,Teruaki, AU - Yamashita,Tomoya, AU - Kobayashi,Kazuyuki, AU - Yokoyama,Mitsuhiro, PY - 2006/8/19/pubmed PY - 2007/1/11/medline PY - 2006/8/19/entrez SP - 546 EP - 56 JF - Respirology (Carlton, Vic.) JO - Respirology VL - 11 IS - 5 N2 - BACKGROUND: Nitric oxide (NO) produced by endothelial NO synthase (eNOS) is thought to effect an anti-inflammatory response, but its mechanism is still unknown. METHODS: eNOS transgenic (eNOS-TG) mice and their littermate controls (C57/BL6) were used to clarify the role of NO derived from eNOS. Bleomycin hydrochloride (1 U/body/day) or PBS was injected intraperitoneally. RESULTS: Subpleural fibrotic changes and hydroxyproline content in the eNOS-TG mice were significantly reduced compared with those of the wild-type (WT) mice by day 56. Administration of N(omega)-nitro-L-arginine methyl ester, a potent inhibitor of NO synthase, worsened the fibrotic response in bleomycin-treated eNOS-TG mice. Gelatinolytic activity in lung homogenates, corresponding to metalloproteinase-9 (MMP-9), was significantly increased in bleomycin-injured WT mice on day 14. In contrast, the level of tissue inhibitor of metalloproteinases-1 (TIMP-1), an endogenous MMP-9 inhibitor, was increased in the bleomycin-treated eNOS-TG mice compared with WT. Immunohistochemical analysis demonstrated that MMP-9 and TIMP-1 were strongly expressed in inflammatory cells, including subpleural fibrotic lesions. CONCLUSION: These data suggested that eNOS overexpression attenuates bleomycin-induced lung injury by ameliorating the MMP-9/TIMP-1 balance. SN - 1323-7799 UR - https://www.unboundmedicine.com/medline/citation/16916326/Overexpression_of_nitric_oxide_synthase_by_the_endothelium_attenuates_bleomycin_induced_lung_fibrosis_and_impairs_MMP_9/TIMP_1_balance_ L2 - https://doi.org/10.1111/j.1440-1843.2006.00894.x DB - PRIME DP - Unbound Medicine ER -