Differential expression of the inflammation-associated chemokines/cytokines in mouse lung after exposure to cigarette smoke and smoking cessation.

ABSTRACT

OBJECTIVE: To determine the changes in the airway inflammation-related cytokine/chemokine profiles after exposure to cigarette smoke (CS) and smoking cessation (SC). METHODS: A total of 18 male C57BL/6 mice were equally divided into three groups CS group, SC group, and normal control group. The airway resistance, lung morphology, and collagen deposition around airways were determined. HE staining and Masson trichrome staining were used for histopathological analysis. The inflammatory cells in bronchoalveolar lavage fluid (BALF) were assessed. The inflammation-associated cytokines were determined using real-time PCR and immunohistochemistry. Expressions of CXCR3 ligands including the CXCL9, CXCL10, CXCL11 and other cytokines in lung tissue and BALF were also analyzed. RESULTS: The airway resistance significantly increased in both CS group and SC group when compared with the normal control group. Lung pathological scores in both CS group and SC group were also higher than that in the normal control group, while there was no significant difference between the CS group and SC group. Inflammatory cells including the neutrophils, macrophages, and lymphocytes also increased in both the CS group and SC group at both mRNA and protein levels. The mRNA levels of CXCL9, CXCL10, MMP9, and MMP12 were significantly higher in CS group and SC group than those in the normal control group (all P<0.05). The protein expression levels of CXCL9, CXCL10, CXCL11, MMP2, MMP9, MMP12, and TGF-Β1 were significantly higher in CS group and SC group than those in the normal control group (all P<0.05). Compared with the normal control group,the concentrations of CXCL9, CXCL10, CXCL11, IL-8, and TGF-Β1 in the BALF supernatants of the CS group and SC group significantly increased (P<0.05); in addition, the IL-6 and TNF-Α concentrations also increased in the CS group (both P<0.05). CONCLUSIONS: CS exposure triggers inflammatory cell flux and accumulation in the lung parenchyma and BALF. As a consequence, the inflammatory cytokines increase dramatically. After CS, the cytokines/chemokines can decrease, but is still higher than in non-smokers.