The PPAR-γ agonist pioglitazone exerts proinflammatory effects in bronchial epithelial cells during acute Pseudomonas aeruginosa pneumonia

Bianca L. Ferreira, Ivan Ramirez-Moral, Natasja A. Otto, Reinaldo Salomão, Alex F. de Vos, Tom van der Poll

Research output: Contribution to journalArticle*Academicpeer-review

Abstract

Pseudomonas aeruginosa is a common respiratory pathogen that causes injurious airway inflammation during acute pneumonia. Peroxisome proliferator-activated receptor (PPAR)-γ is involved in the regulation of metabolic and inflammatory responses in different cell types and synthetic agonists of PPAR-γ exert anti-inflammatory effects on myeloid cells in vitro and in models of inflammation in vivo. We sought to determine the effect of the PPAR-γ agonist pioglitazone on airway inflammation induced by acute P. aeruginosa pneumonia, focusing on bronchial epithelial cells. Mice pretreated with pioglitazone or vehicle (24 and 1 h) were infected with P. aeruginosa via the airways. Pioglitazone treatment was associated with increased expression of chemokine (Cxcl1, Cxcl2, and Ccl20) and cytokine genes (Tnfa, Il6, and Cfs3) in bronchial brushes obtained 6 h after infection. This pro-inflammatory effect was accompanied by increased expression of Hk2 and Pfkfb3 genes encoding rate-limiting enzymes of glycolysis; concurrently, the expression of Sdha, important for maintaining metabolite flux in the tricarboxylic acid cycle, was reduced in bronchial epithelial cells of pioglitazone treated-mice. Pioglitazone inhibited bronchoalveolar inflammatory responses measured in lavage fluid. These results suggest that pioglitazone exerts a selective proinflammatory effect on bronchial epithelial cells during acute P. aeruginosa pneumonia, possibly by enhancing intracellular glycolysis.
Original languageEnglish
Pages (from-to)370-377
Number of pages8
JournalClinical and Experimental Immunology
Volume207
Issue number3
DOIs
Publication statusPublished - 12 May 2022

Keywords

  • Pseudomonas aeruginosa
  • inflammation
  • innate immunity
  • pioglitazone

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