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Viruses. 2019 Jun 1;11(6). pii: E505. doi: 10.3390/v11060505.
Peroxisome Proliferator-Activated Receptor Gamma (PPAR) Suppresses Inflammation and Bacterial Clearance during Influenza-Bacterial Super-Infection.
Gopal R1, Mendy A2, Marinelli MA3, Richwalls LJ4, Seger PJ5, Patel S6, McHugh KJ7, Rich HE8, Grousd JA9, Forno E10, Alcorn JF11.
Author information
Abstract
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 PPARγagonists (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.
KEYWORDS:
MRSA; PPAR agonist; chemokines; cytokines; lung; neutrophils; pneumonia; rosiglitazone
PMID: 31159430 DOI: 10.3390/v11060505
Free full text
Peroxisome Proliferator-Activated Receptor Gamma (PPAR) Suppresses Inflammation and Bacterial Clearance during Influenza-Bacterial Super-Infection.
Gopal R1, Mendy A2, Marinelli MA3, Richwalls LJ4, Seger PJ5, Patel S6, McHugh KJ7, Rich HE8, Grousd JA9, Forno E10, Alcorn JF11.
Author information
Abstract
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 PPARγagonists (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.
KEYWORDS:
MRSA; PPAR agonist; chemokines; cytokines; lung; neutrophils; pneumonia; rosiglitazone
PMID: 31159430 DOI: 10.3390/v11060505
Free full text