Abstract
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-1 β, 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.Keywords: Rosiglitazone, PPAR-γ, IL-6, IL-8, Acute lung injury
Highlights
Various cytokines and inflammatory mediators participate in inflammatory response of acute lung injury (ALI)
Inoue et al disclosed that 15-deoxy∆12,14-prostaglandin J2 (15d-PGJ2), a Peroxisome proliferator-activated receptor (PPAR)-γ ligand, did not improve but significantly enhanced ALI induced by lipopolysaccharide in the mouse [22]
We identified that rosiglitazone could directly induce the expression of PPAR-γ in alveolar and bronchial epithelial cells, resident tissue cells of lung
Summary
Various cytokines and inflammatory mediators participate in inflammatory response of acute lung injury (ALI). Alveolar and bronchial epithelial cells are major target cells of inflammatory response of ALI, they can act as effector cells secreting IL-6 and IL-8. These two cells are pivotal in the pathophysiology of ALI [2,3]. PPAR-γ is expressed mainly in adipose tissues and plays a role in differentiation of adipocytes [7]. PPAR-γ is expressed in airway smooth muscles, airway epithelial cells, and alveolar macrophages [8,9]. It is known that binding of ligand to PPAR-γ inhibits inflammatory genes by regulating another transcriptional factor, such as NF-κB (nuclear factor kappa B) [13]
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