title: Impacts of peroxisome proliferator-activated receptor-γ activation on cigarette smoke-induced exacerbated response to bacteria.
abstract: Chronic obstructive pulmonary disease (COPD) is characterised by a state of chronic pulmonary inflammation punctuated by microbial exacerbations. Despite advances in treatment options, COPD remains difficult to manage. In this study, we investigated the potential of peroxisome proliferator-activated receptor (PPAR)γ activation as a new therapy against cigarette smoke-induced inflammation and its associated bacterial exacerbation. C57BL/6 mice were exposed to room air or cigarette smoke for either 4 days or 4 weeks and treated either prophylactically or therapeutically with rosiglitazone. The impact of rosiglitazone on cigarette smoke-induced exacerbated response to the bacterial pathogen nontypeable Haemophilus influenzae (NTHi) was studied using the therapeutic treatment protocol. We found that rosiglitazone was able to reduce cigarette smoke-induced neutrophilia both when administered prophylactically or therapeutically. Therapeutic intervention with rosiglitazone was also effective in preventing cigarette smoke-induced neutrophilia exacerbation following NTHi infection. Moreover, the anti-inflammatory effects of rosiglitazone did not lead to an increase in the pulmonary bacterial burden, unlike dexamethasone. Altogether, our data suggest that pharmacological activation of PPARγ may be an effective therapeutic approach to improve COPD management, as it is able to reduce cigarette smoke-induced inflammation and decrease the magnitude of bacterial exacerbations, without compromising the ability of the immune system to control the infection.
authors.affiliation: Dept of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.
authors.forename: Mathieu C
authors.initials: MC
authors.lastname: Morissette
authors.affiliation: Medical Sciences Graduate Program, McMaster University, Hamilton, ON, Canada.
authors.forename: Pamela
authors.initials: P
authors.lastname: Shen
authors.affiliation: Honours Molecular Biology and Genetics Co-op Program, McMaster University, Hamilton, ON, Canada.
authors.forename: Danya
authors.initials: D
authors.lastname: Thayaparan
authors.affiliation: Dept of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada Dept of Medicine, Firestone Institute of Respiratory Health, St. Joseph's Healthcare, McMaster University, Hamilton, ON, Canada stampfli@mcmaster.ca.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Stämpfli
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000818:Animals; D001424:Bacterial Infections / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D008168:Lung / Q000187:drug effects* / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects; D047495:PPAR gamma / Q000378:metabolism*; D011014:Pneumonia / Q000188:drug therapy; D029424:Pulmonary Disease, Chronic Obstructive / Q000382:microbiology; D000077154:Rosiglitazone; D012907:Smoking / Q000009:adverse effects*; D045162:Thiazolidinediones / Q000494:pharmacology; D062789:Tobacco Products
chemical_list: D000305:Adrenal Cortex Hormones; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D003907:Dexamethasone