Purpose: Peroxisome proliferator-activated receptor (PPAR)-γ ligand is known to repress the expression of pro-inflammatory mediators. However, it is unclear how it affects PPAR-γ expression and the inflammatory response in the human lung. We investigated the effects of rosiglitazone (synthetic PPAR-γ ligand) on the PPAR-γ expression and on the IL-6 and IL-8 production in acute lung injury model using human lung epithelial cells.
Methods: A549 and Beas-2B cells were pre-treated with rosiglitazone and/or BADGE (selective PPAR-γ antagonist) and then treated with media control or cytokine mixture including TNF-α, IL-1β, and IFN-γ. PPAR-γ expression was analyzed in cell lysates by Western blot. IL-6 and IL-8 production was measured in the culture supernatants by ELISA.
Results: PPAR-γ expression was identified in all experimental groups except for the control. The cytokine mixture-induced IL-6 and IL-8 production was significantly inhibited by pre-treatment with rosiglitazone (P<0.01). However, this inhibitory effect of rosiglitazone was not reversed by BADGE.
Conclusion: These suggest that rosiglitazone induces the PPAR-γ expression and it may inhibit the cytokine mixture-induced IL-6 and IL-8 production through the PPAR-γ independent pathway. The inhibitory mechanisms of rosiglitazone on the cytokine mixture-induced IL-6 and IL-8 production in human alveolar and bronchial epithelial cells remain to be further investigated.