In:
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Physiological Society, Vol. 290, No. 1 ( 2006-01), p. R126-R133
Abstract:
We reported previously that mice obese as a result of leptin deficiency ( ob/ ob) have enhanced ozone (O 3 )-induced airway hyperresponsiveness (AHR) and inflammation compared with wild-type (C57BL/6) controls. To determine whether this increased response to O 3 was independent of the modality of obesity, we examined O 3 -induced AHR and inflammation in Cpe fat mice. These mice are obese as a consequence of a mutation in the gene encoding carboxypeptidase E (Cpe), an enzyme important in processing prohormones and proneuropeptides involved in satiety and energy expenditure. Airway responsiveness to intravenous methacholine, measured by forced oscillation, was increased in Cpe fat vs. wild-type mice after air exposure. In addition, compared with air exposure, airway responsiveness was increased 24 h after O 3 exposure (2 ppm for 3 h) in Cpe fat but not in wild-type mice. Compared with air-exposed controls, O 3 exposure increased bronchoalveolar lavage fluid (BALF) protein, IL-6, KC, MIP-2, MCP-1, and soluble TNF receptors (sTNFR1 and sTNFR2) as well as BALF neutrophils. With the exception of sTNFR1 and sTNFR2, all of these outcome indicators were greater in Cpe fat vs. wild-type mice. Serum sTNFR1, sTNFR2, MCP-1, leptin, and blood leukocytes were elevated in Cpe fat compared with wild-type mice even in the absence of O 3 exposure, similar to the chronic systemic inflammation observed in human obesity. These results indicate that increased O 3 -induced AHR and inflammation are consistent features of obese mice, regardless of the modality of obesity. These results also suggest that chronic systemic inflammation may enhance airway responses to O 3 in obese mice.
Type of Medium:
Online Resource
ISSN:
0363-6119
,
1522-1490
DOI:
10.1152/ajpregu.00306.2005
Language:
English
Publisher:
American Physiological Society
Publication Date:
2006
detail.hit.zdb_id:
1477297-8
SSG:
12
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