Pentoxifylline attenuates cigarette smoke-induced overexpression of CXCR3 and IP-10 in mice
10.3760/cma.j.issn.0366-6999.2012.11.026
- Author:
Zheng WANG
1
;
Yan-Wei CHEN
;
Jin-Nong ZHANG
;
Xiao-Fei HU
;
Mei-Jun PENG
Author Information
1. Department of Respiratory Medicine, No.1 Hospital of Hefei City, Anhui 230061, China
- Keywords:
pentoxifylline;
cigarette smoke;
pulmonary emphysema,CXCR3;
interferon-inducible protein- 10
- From:
Chinese Medical Journal
2012;(11):1980-1985
- CountryChina
- Language:Chinese
-
Abstract:
Background Cigarette smoke-induced emphysema is associated with overexpression of the chemokine receptor CXCR3 and its ligands.Previously,we have demonstrated that pentoxifylline (PTX) alleviated cigarette smoke-induced emphysema.The aim of this study was to determine if the overexpression of CXCR3 and its ligand interferon-inducible protein-10 (IP-10) that was elicited by smoke exposure were attenuated by PTX.Methods (1) The study in vitro:a given number of RAW264.7 macrophages with decreasing concentrations of PTX in the culture medium were challenged with cigarette smoke extract (CSE); (2) The study in vivo:male BALB/c mice were randomized into four groups,i.e.,sham-smoke,smoke only,smoke with 2 mg/kg PTX,and smoke with 10 mg/kg PTX.The smoke exposure time was 90 minutes once a day,6 days a week for 16 weeks.PTX was given intraperitoneally before each episode of smoke exposure.Interferon (IFN)-y and IP-10 in broncho-alveolar lavage fluid (BALF) and in culture medium were measured by enzyme-linked immunosorbent assay (ELISA).IP-10 mRNA in lung tissue was assessed by RT-PCR.CXCR3 positive cells in lung sections were visualized by immunochemistry staining.Results Up-regulation of IFN-y and IP-10 in the culture medium of macrophages elicited by CSE was inhibited by PTX in a dose-dependent manner.Chronic cigarette smoke exposure led to overexpression of IFN-y and IP-10 in BALF,upregulation of IP-10 mRNA and increased infiltration of CXCR3+ cells into lung parenchyma.Administration of PTX decreased the level of IFN-y from (6.26±1.38) ng/ml to (4.43±0.66) ng/ml by low dose PTX or to (1.74±0.28) ng/ml by high dose PTX.IP-10 was reduced from (10.35±1.49) ng/ml to (8.19±0.79) ng/ml by low dose PTX or to (7.51±0.60)ng/ml by high dose PTX.The expression of IP-10 mRNA was also down-regulated (P ＜0.05).But only with a high dose of PTX was the ratio of CXCR3+ cells decreased; 15.2±7.3 vs.10.4±1.8 (P ＜0.05).Conclusion PTX attenuates cigarette smoke-induced overexpression of chemokine receptor CXCR3 and its ligand IP-10,which is relevant to its inhibitory effect on pulmonary emphysema.
