Journalartikel

Jahr der Veröffentlichung: 2015

Seiten: 393-403

Zeitschrift: Experimental Lung Research

Bandnummer: 41

Heftnummer: 7

ISSN: 0190-2148

eISSN: 1521-0499

DOI Link: https://doi.org/10.3109/01902148.2015.1046200

Verlag: Taylor and Francis Group

Abstract: 
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- (PPAR-) by fibrates, such as WY-14643 (WY), has been described to beneficially influence inflammation and experimental lung injury. The impact of PPAR- activation on alveolar epithelial cells (AEC) has not been studied yet. Materials and Methods: To investigate the effect of PPAR- activator WY in wild-type (WT) and in PPAR- knockout (PPAR-(-/-)) animals, mice were treated in different regimes: mice received chow enriched with or without WY for 14days 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-, MIP-2, and TxB(2) after LPS stimulation. This beneficial effect was abrogated in PPAR-(-/-) 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- activation. PGE(2) concentration remained high after LPS challenge and was unaffected by WY treatment. Conclusion: PPAR- 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- activation into clinical therapy of ARDS.

Harvard-Zitierstil: Hecker, M., Behnk, A., Morty, R., Sommer, N., Vadasz, I., Herold, S., et al. (2015) PPAR-α activation reduced LPS-induced inflammation in alveolar epithelial cells, Experimental Lung Research, 41(7), pp. 393-403. https://doi.org/10.3109/01902148.2015.1046200

APA-Zitierstil: Hecker, M., Behnk, A., Morty, R., Sommer, N., Vadasz, I., Herold, S., Seeger, W., & Mayer, K. (2015). PPAR-α activation reduced LPS-induced inflammation in alveolar epithelial cells. Experimental Lung Research. 41(7), 393-403. https://doi.org/10.3109/01902148.2015.1046200