Ryohei Miyata1, Ni Bai2, Renaud Vincent3, Don D Sin1, Stephan F Van Eeden4. 1. UBC James Hogg Research Centre, Institute for Heart + Lung Health, St. Paul's Hospital, The University of British Columbia, Vancouver, BC. 2. UBC James Hogg Research Centre, Institute for Heart + Lung Health, St. Paul's Hospital, The University of British Columbia, Vancouver, BC; Department of Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, Vancouver, BC. 3. Environmental Health, Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, ON, Canada. 4. UBC James Hogg Research Centre, Institute for Heart + Lung Health, St. Paul's Hospital, The University of British Columbia, Vancouver, BC. Electronic address: Stephan.vanEeden@hli.ubc.ca.
Abstract
BACKGROUND: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) suppress ambient particulate matter, 10 μm (PM(10) )-induced inflammatory response in vitro. The aim of this study was to determine the effect of statins on PM(10) -induced lung inflammation in vivo. METHODS: New Zealand white rabbits were exposed to either PM(10) (1.0 mg/kg) or saline by direct intratracheal instillation three times a week for 4 weeks lovastatin 5.0 mg/kg/d. BAL fluid was assessed for cell counts and proinflammatory cytokine levels. Lung inflammation was quantified using immunohistochemical techniques and morphometric methods. Ex vivo phagocytosis assay of alveolar macrophages using PM 10 particles was performed. Distribution of PM(10) particles in lung tissues and draining lymph nodes was quantified morphometrically to evaluate the clearance of PM(10) particles. RESULTS: PM(10) exposure increased the production of IL-6 and IL-8, promoted the recruitment of macrophages and polymorphonuclear leukocytes into the lung, and activated these recruited leukocytes. Lovastatin significantly suppressed all these effects. Lovastatin increased the phagocytic activity of macrophages and promoted the migration of PM 10 -laden macrophages to the regional lymph nodes. CONCLUSIONS: Lovastatin attenuates the PM(10) -induced recruitment and activation of alveolar macrophages and polymorphonuclear leukocytes, reduces local proinflammatory cytokine production, and promotes the clearance of PM(10) particles from lung tissues to regional lymph nodes. These novel pleiotropic properties of statins are most likely to contribute to the downregulation of PM(10) -induced lung inflammation.
BACKGROUND: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) suppress ambient particulate matter, 10 μm (PM(10) )-induced inflammatory response in vitro. The aim of this study was to determine the effect of statins on PM(10) -induced lung inflammation in vivo. METHODS: New Zealand white rabbits were exposed to either PM(10) (1.0 mg/kg) or saline by direct intratracheal instillation three times a week for 4 weeks lovastatin 5.0 mg/kg/d. BAL fluid was assessed for cell counts and proinflammatory cytokine levels. Lung inflammation was quantified using immunohistochemical techniques and morphometric methods. Ex vivo phagocytosis assay of alveolar macrophages using PM 10 particles was performed. Distribution of PM(10) particles in lung tissues and draining lymph nodes was quantified morphometrically to evaluate the clearance of PM(10) particles. RESULTS: PM(10) exposure increased the production of IL-6 and IL-8, promoted the recruitment of macrophages and polymorphonuclear leukocytes into the lung, and activated these recruited leukocytes. Lovastatin significantly suppressed all these effects. Lovastatin increased the phagocytic activity of macrophages and promoted the migration of PM 10 -laden macrophages to the regional lymph nodes. CONCLUSIONS:Lovastatin attenuates the PM(10) -induced recruitment and activation of alveolar macrophages and polymorphonuclear leukocytes, reduces local proinflammatory cytokine production, and promotes the clearance of PM(10) particles from lung tissues to regional lymph nodes. These novel pleiotropic properties of statins are most likely to contribute to the downregulation of PM(10) -induced lung inflammation.
Authors: Dai-Hua Tsai; Michael Riediker; Antoine Berchet; Fred Paccaud; Gerard Waeber; Peter Vollenweider; Murielle Bochud Journal: Environ Sci Pollut Res Int Date: 2019-05-12 Impact factor: 4.223
Authors: Adam M Speen; Hye-Young H Kim; Rebecca N Bauer; Megan Meyer; Kymberly M Gowdy; Michael B Fessler; Kelly E Duncan; Wei Liu; Ned A Porter; Ilona Jaspers Journal: J Biol Chem Date: 2016-10-04 Impact factor: 5.157
Authors: Esmée Bijnens; Nicky Pieters; Harrie Dewitte; Bianca Cox; Bram G Janssen; Nelly Saenen; Evi Dons; Maurice P Zeegers; Luc Int Panis; Tim S Nawrot Journal: BMC Public Health Date: 2013-12-23 Impact factor: 3.295