Role of peroxisome proliferator activator receptor-gamma (PPAR-γ) in lung sepsis

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Usha Q Patel; Grazia V Clemencet; Colleen B Latruffe; Peter A Reddy; Qin Chu; Charlene J Heyman; Alice E Griffin 

AJBM  Volume 2, Issue 3, pages 270–291, March 2014             Full Text-PDF


Abstract

PPAR-gamma has been implicated in the pathology of numerous diseases including; obesity, diabetes, atherosclerosis, and cancer. PPAR-gamma agonists have been used in the treatment of hyperlipidaemia and hyperglycemia. Two isoform of PPARG are detected in the human and in the mouse: PPAR-γ1 (found in nearly all tissues except muscle) and PPAR-γ2 (mostly found in adipose tissue and the intestine). In the present study, to directly determine the role of PPARγ in lung sepsis we used PPARγ-knockout and C57/BL6 mice model. Mice are treated with Lipopolysaccharide LPS (0.5 mg/kg, iv) for 6-hours, the plasma and tissue cytokines TNF-α, IL-1β, IL-6, IL-10, MIP-1 and KC are analyzed by ELISA. The infiltrations of the mononuclear cells in the lung tissue and degree of lung tissue injury are examined using immunofluorescent and histopathology staining respectively. In PPARγ-knockout mice, LPS induced more expression of pro-inflammatory cytokines expression, which was associated with a marked monocyte infiltration, tissue injury and elevated lung activity of myeloperoxidase compared with wild type C57/BL6 mice. Present study, suggests that PPARγ has a critical role in attenuate lung sepsis and further study need to elucidate the clinical value.

Keywords: PPARγ; LPS; Proinflammatory cytokines; Lung; Immunofluorescent; PPARγ-knockout mice


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