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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook 2016     Display Documents



ID: 723989.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook 2016
PPAR-alpha activation reduced LPS-induced inflammation in alveolar epithelial cells
Authors:Hecker, M.; Behnk, A.; Morty, R. E.; Sommer, N.; Vadasz, I.; Herold, S.; Seeger, W.; Mayer, K.
Date of Publication (YYYY-MM-DD):2015
Title of Journal:Exp Lung Res
Volume:41
Issue / Number:7
Start Page:393
End Page:403
Audience:Not Specified
Abstract / Description:PURPOSE OF THE STUDY: Acute respiratory distress syndrome (ARDS) represents a major cause of mortality in intensive care patients. Activation of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) by fibrates, such as WY-14643 (WY), has been described to beneficially influence inflammation and experimental lung injury. The impact of PPAR-alpha activation on alveolar epithelial cells (AEC) has not been studied yet. MATERIALS AND METHODS: To investigate the effect of PPAR-alpha activator WY in wild-type (WT) and in PPAR-alpha knockout (PPAR-alpha(-/-)) animals, mice were treated in different regimes: mice received chow enriched with or without WY for 14 days prior AEC isolation (in-vivo treatment). Furthermore, isolated AEC from both groups were subsequently cultured with or without WY (in-vitro treatment). AEC were stimulated with lipopolysaccharide (LPS). Cell culture supernatant and cell lysate were used for analysis of pro-inflammatory mediators. RESULTS: AEC challenged with LPS showed a significantly increased generation of pro-inflammatory mediators. After in-vivo WY-exposure, AEC displayed significantly reduced concentration of TNF-alpha, MIP-2, and TxB2 after LPS stimulation. This beneficial effect was abrogated in PPAR-alpha(-/-) animals. Interestingly, sole in-vitro application of WY-14643 failed to reduce levels of pro-inflammatory mediators whereas we found an additive effect of a combined in-vivo and in-vitro PPAR-alpha activation. PGE2 concentration remained high after LPS challenge and was unaffected by WY treatment. CONCLUSION: PPAR-alpha activation by in-vivo exposure to fibrates reduced the inflammatory response in isolated AEC. These findings may facilitate further studies investigating the translation of pharmacological PPAR-alpha activation into clinical therapy of ARDS.
Free Keywords:acute lung injury; alveolar epithelial cells; fibrate; inflammation; peroxisome proliferator-activated receptor-alpha
External Publication Status:published
Document Type:Article
Communicated by:n.n.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:b 2 Department of Lung Development and Remodelling , Max Planck Institute for Heart and Lung Research , Bad Nauheim, Germany.
Identifiers:ISSN:1521-0499 (Electronic) 0190-2148 (Linking) %R 10.3109/01902148.2015.1046200
URL:http://www.ncbi.nlm.nih.gov/pubmed/26151160
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