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Hypercapnic Emphysema in C3H Mice Induced by Cigarette Smoke (CS) Demonstrates Pulmonary Inflammation Concomitant With Increased Matrix Metalloproteinases (MMPs) and Substance P (SP)
Author(s) -
Xu Junyang,
Xu Fadi,
Wang Rurong,
Seagrave JeanClare,
March Thomas H.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a209-b
Subject(s) - matrix metalloproteinase , copd , inflammation , lung , medicine , pathogenesis , substance p , mmp3 , pathology , hypercapnia , immunology , receptor , respiratory system , chemistry , gene expression , biochemistry , gene , neuropeptide
We have recently established a model of CS‐induced emphysema in C3H mice characterized by hypercapnia and depressed ventilatory response that closely resembles the major features of patients with hypercapnic chronic obstructive pulmonary disease (COPD). COPD is often associated with pulmonary inflammation. Previous studies have shown that increased MMP activity, IL‐1β and SP are involved in inflammatory process, and the former two may be involved in pulmonary parenchymal destruction associated with emphysema and the latter is implicated in airway remodeling. Therefore, we asked whether this animal model has pulmonary inflammation, and if so, whether MMPs, IL‐1β, SP and its receptor (neurokinin A receptor, NK1R) were altered. The mice were exposed to CS (100 mg TPM/m 3 in the first wk and 250 mg for the following wks) or filtered air for 16 wks. After exposure, pulmonary MMP‐ 2, 9, and 12 were detected by RT‐PCR and the activity of MMP‐2 and‐9 was assessed by zymography, IL‐1β was measured by ELISA, and SP and NK1R were analyzed by EIA and RT‐PCR, respectively. We found that CS‐induced emphysema was associated with pulmonary inflammation characterized by infiltrates of macrophages, neutrophils and lymphocytes. CS also significantly upregulated: (a) SP level and expression of NK1 mRNA; (b) MMP2, 9 and 12 mRNA expressions and MMP‐2 and ‐9 enzymatic activity; and (c) IL‐1β in lung tissues. Our data confirm the pulmonary inflammation and suggest that the observed elevation of MMPs, IL‐1β, SP and NK1R may be involved in pathogenesis of emphysema in this model. (Supported by ALA CI‐016N and NIH 74183)