{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:04:24Z","timestamp":1790125464812,"version":"4.0.1"},"reference-count":62,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T00:00:00Z","timestamp":1559347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL107380"],"award-info":[{"award-number":["R01HL107380"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["K08HL125666"],"award-info":[{"award-number":["K08HL125666"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Influenza virus is among the most common causes of respiratory illness worldwide and can be complicated by secondary bacterial pneumonia, a frequent cause of mortality. When influenza virus infects the lung, the innate immune response is activated, and interferons and inflammatory mediators are released. This \u201ccytokine storm\u201d is thought to play a role in influenza-induced lung pathogenesis. Peroxisome proliferator-activated receptor gamma (PPAR\u03b3) is a member of the nuclear hormone receptor super-family. PPAR\u03b3 has numerous functions including enhancing lipid and glucose metabolism and cellular differentiation and suppressing inflammation. Synthetic PPAR\u03b3 agonists (thiazolidinediones or glitazones) have been used clinically in the treatment of type II diabetes. Using data from the National Health and Nutrition Examination Survey (NHANES), diabetic participants taking rosiglitazone had an increased risk of mortality from influenza\/pneumonia compared to those not taking the drug. We examined the effect of rosiglitazone treatment during influenza and secondary bacterial (Methicillin resistant Staphylococcus aureus) pneumonia in mice. We found decreased influenza viral burden, decreased numbers of neutrophils and macrophages in bronchoalveolar lavage, and decreased production of cytokines and chemokines in influenza infected, rosiglitazone-treated mice when compared to controls. However, rosiglitazone treatment compromised bacterial clearance during influenza-bacterial super-infection. Both human and mouse data suggest that rosiglitazone treatment worsens the outcome of influenza-associated pneumonia.<\/jats:p>","DOI":"10.3390\/v11060505","type":"journal-article","created":{"date-parts":[[2019,6,3]],"date-time":"2019-06-03T02:08:40Z","timestamp":1559527720000},"page":"505","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Peroxisome Proliferator-Activated Receptor Gamma (PPAR\u03b3) Suppresses Inflammation and Bacterial Clearance during Influenza-Bacterial Super-Infection"],"prefix":"10.3390","volume":"11","author":[{"given":"Radha","family":"Gopal","sequence":"first","affiliation":[{"name":"Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelico","family":"Mendy","sequence":"additional","affiliation":[{"name":"College of Public Health, University of Iowa, Iowa City, IA 52246, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Marinelli","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lacee J.","family":"Richwalls","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip J.","family":"Seger","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivani","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J.","family":"McHugh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen E.","family":"Rich","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7418-4741","authenticated-orcid":false,"given":"Jennifer A.","family":"Grousd","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erick","family":"Forno","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Alcorn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/nri3665","article-title":"Innate immunity to influenza virus infection","volume":"14","author":"Iwasaki","year":"2014","journal-title":"Nat. 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