Rosiglitazone ameliorated airway inflammation induced by cigarette smoke via inhibiting the M1 macrophage polarization by activating PPARγ and RXRα

Rosiglitazone, an exogenous ligand of PPARγ, plays an important anti-inflammatory role during the inflammation caused by cigarette smoke (CS). CS exposure induces pulmonary inflammation via activating macrophage polarization. However, the effects of rosiglitazone on macrophage polarization induced by CS are unclear.

Rosiglitazone ameliorated the emphysema and inflammation in lung tissues induced by CS exposure via inhibiting the M1 macrophage polarization through activating PPARγ and RXRα.

36 male Wistar rats were randomly divided into 3 groups: control, CS and ROSI. In the CS group, rats were passively exposed to cigarette smoke for consecutive 3 months. In the ROSI group, rats were treated with rosiglitazone (3 mg/kg/day, ip) during CS exposure period. Alveolar macrophages of rats were isolated and cultured with CSE. The slices of lung tissues were stained with hematoxylin and eosin. The histomorphology was observed to evaluate emphysema and the pulmonary function was detected. Cells in bronchoalveolar lavage fluid (BALF) were examined and the expression of cytokines TNF-α and IL-1β was detected by ELISA and qPCR. The alveolar macrophage polarization was evaluated by immunohistochemistry and flow cytometry assay in vivo and by qPCR in vitro. The protein level of PPARγ and RXRα was measured by Western blot.

CS exposure induced significant emphysema, diminished FEV0.2/FVC, elevated PEF, and higher level of total cells, neutrophils and cytokines (TNF-α and IL-1β) in BALF compared with control group, whereas rosiglitazone partly ameliorated above disorders. CS exposure activated M1 and M2 macrophage polarization in vivo and in vitro, whereas rosiglitazone inhibited CS induced M1 macrophage polarization and decreased the ratio of M1/M2. The effects of rosiglitazone on macrophage polarization were partly blocked after AMs treated with the antagonists of PPARγ and RXRα, and were synergistically enhanced by the agonist of RXRα. CS exposure decreased the expression of PPARγ and RXRα in lung tissues and AMs, and rosiglitazone partly reversed CS-mediated suppression of PPARγ and RXRα.