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Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Suppresses Inflammation and Bacterial Clearance during Influenza-Bacterial Super-Infection

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 rele...

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Autores principales: Gopal, Radha, Mendy, Angelico, Marinelli, Michael A., Richwalls, Lacee J., Seger, Philip J., Patel, Shivani, McHugh, Kevin J., Rich, Helen E., Grousd, Jennifer A., Forno, Erick, Alcorn, John F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630660/
https://www.ncbi.nlm.nih.gov/pubmed/31159430
http://dx.doi.org/10.3390/v11060505
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author Gopal, Radha
Mendy, Angelico
Marinelli, Michael A.
Richwalls, Lacee J.
Seger, Philip J.
Patel, Shivani
McHugh, Kevin J.
Rich, Helen E.
Grousd, Jennifer A.
Forno, Erick
Alcorn, John F.
author_facet Gopal, Radha
Mendy, Angelico
Marinelli, Michael A.
Richwalls, Lacee J.
Seger, Philip J.
Patel, Shivani
McHugh, Kevin J.
Rich, Helen E.
Grousd, Jennifer A.
Forno, Erick
Alcorn, John F.
author_sort Gopal, Radha
collection PubMed
description 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 “cytokine storm” is thought to play a role in influenza-induced lung pathogenesis. Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the nuclear hormone receptor super-family. PPARγ has numerous functions including enhancing lipid and glucose metabolism and cellular differentiation and suppressing inflammation. Synthetic PPARγ 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.
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spelling pubmed-66306602019-08-19 Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Suppresses Inflammation and Bacterial Clearance during Influenza-Bacterial Super-Infection Gopal, Radha Mendy, Angelico Marinelli, Michael A. Richwalls, Lacee J. Seger, Philip J. Patel, Shivani McHugh, Kevin J. Rich, Helen E. Grousd, Jennifer A. Forno, Erick Alcorn, John F. Viruses Article 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 “cytokine storm” is thought to play a role in influenza-induced lung pathogenesis. Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the nuclear hormone receptor super-family. PPARγ has numerous functions including enhancing lipid and glucose metabolism and cellular differentiation and suppressing inflammation. Synthetic PPARγ 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. MDPI 2019-06-01 /pmc/articles/PMC6630660/ /pubmed/31159430 http://dx.doi.org/10.3390/v11060505 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gopal, Radha
Mendy, Angelico
Marinelli, Michael A.
Richwalls, Lacee J.
Seger, Philip J.
Patel, Shivani
McHugh, Kevin J.
Rich, Helen E.
Grousd, Jennifer A.
Forno, Erick
Alcorn, John F.
Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Suppresses Inflammation and Bacterial Clearance during Influenza-Bacterial Super-Infection
title Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Suppresses Inflammation and Bacterial Clearance during Influenza-Bacterial Super-Infection
title_full Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Suppresses Inflammation and Bacterial Clearance during Influenza-Bacterial Super-Infection
title_fullStr Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Suppresses Inflammation and Bacterial Clearance during Influenza-Bacterial Super-Infection
title_full_unstemmed Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Suppresses Inflammation and Bacterial Clearance during Influenza-Bacterial Super-Infection
title_short Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Suppresses Inflammation and Bacterial Clearance during Influenza-Bacterial Super-Infection
title_sort peroxisome proliferator-activated receptor gamma (pparγ) suppresses inflammation and bacterial clearance during influenza-bacterial super-infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630660/
https://www.ncbi.nlm.nih.gov/pubmed/31159430
http://dx.doi.org/10.3390/v11060505
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