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The adaptive immune response mediated by T lymphocytes is a well‑established factor in the pathogenesis of pulmonary inflammation. Changes in the expression of various connexins (Cxs) or disruption of connexin‑mediated cellular communication in T lymphocytes contribute to inflammation or tissue remodeling. The aim of the present study was to investigate the potential therapeutic value of blocking Cxs in a monocrotaline (MCT)‑induced pulmonary inflammation rat model. Carbenoxolone (CBX) was used to inhibit connexin‑mediated cellular communication. An MCT rat model was established by intraperitoneal (i.p.) injection of a single dose of MCT (60 mg/kg), and CBX treatment (20 µg/kg/day, i.p.) was initiated on the day following MCT treatment for 28 days. Vehicle‑treated male Sprague‑Dawley rats were used as the negative control. The MCT rat model was evaluated by measuring the pulmonary artery ow acceleration time and right ventricular hypertrophy index (RVHI). Histopathological features of the lung tissues and pulmonary arteriolar remodeling were assessed. The proportions of T lymphocyte subtypes, Cx40/cx43 expression in the T cell subtypes and the cytokine levels in the plasma and the lung tissues were also analyzed. Pharmacological inhibition of Cxs using CBX attenuated MCT‑induced right ventricular hypertrophy, pulmonary arteriolar remodeling, lung brosis and inammatory cell inltration by decreasing the RVHI, pulmonary arterial wall thickening, collagen deposition and pro‑inflammatory cytokines production as well as CD3+ and CD4+ T cell accumulation in lung tissues of MCT‑treated rats. Furthermore, flow cytometry analysis revealed that CBX may inhibit MCT‑induced Cx40 and Cx43 expression in CD4+ and CD8+ T lymphocytes in lung tissues. The present study provides evidence that pharmacological inhibition of Cxs may attenuate MCT‑induced pulmonary arteriolar remodeling and pulmonary inflammatory response, at least in part, by decreasing Cx expression. The results highlight the critical role of Cxs in T lymphocytes in the MCT‑induced pulmonary inflammatory response and that targeting of Cxs may be a potential therapeutic method for treating pulmonary inflammatory diseases.

international journal of molecular medicine

Carbenoxolone decreases monocrotaline‑induced pulmonary inflammation and pulmonary arteriolar remodeling in rats by decreasing the expression of connexins in T lymphocytes