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Soluble epoxide hydrolase inhibitors (sEHIs) demonstrated anti-inflammatory properties in a rat model after acute exposure to tobacco smoke. We compared the efficacy of sEHI t-TUCB (trans-4-{4-[3-(4-trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy}-benzoic acid) and the phosphodiesterase-4 (PDE4) inhibitor Rolipram (Biomol International, Enzo Life Sciences, Farmingdale, NY) to reduce lung injury and inflammation after subacute exposure to tobacco smoke over a period of 4 weeks. Pulmonary physiology, bronchoalveolar lavage, cytokine production, and histopathology were analyzed to determine the efficacy of sEHI and Rolipram to ameliorate tobacco smoke\u2013induced inflammation and injury in the spontaneously hypertensive rat. Both t-TUCB and Rolipram inhibited neutrophil elevation in bronchoalveolar lavage. sEHI t-TUCB suppressed IFN-\u03b3, while improving lung function by reducing tobacco smoke\u2013induced total respiratory resistance and tissue damping (small-airway and peripheral tissue resistance). Increases in tobacco smoke\u2013induced alveolar airspace size were attenuated by t-TUCB. Rolipram inhibited the production of airway mucus. Both t-TUCB and Rolipram inhibited vascular remodeling\u2013related growth factor. These findings suggest that sEHI t-TUCB has therapeutic potential for treating COPD by improving lung function and attenuating the lung inflammation and emphysematous changes caused by tobacco smoke. To the best of our knowledge, this is the first report to demonstrate that sEHI exerts significant protective effects after repeated, subacute tobacco smoke\u2013induced lung injury in a rat model of COPD.<\/jats:p>","DOI":"10.1165\/rcmb.2011-0359oc","type":"journal-article","created":{"date-parts":[[2011,12,16]],"date-time":"2011-12-16T22:48:37Z","timestamp":1324075717000},"page":"614-622","source":"Crossref","is-referenced-by-count":48,"title":["Use of a Soluble Epoxide Hydrolase Inhibitor in Smoke-Induced Chronic Obstructive Pulmonary Disease"],"prefix":"10.1093","volume":"46","author":[{"given":"Lei","family":"Wang","sequence":"first","affiliation":[{"name":"Center for Health and the Environment, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Entomology and Cancer Center, University of California at Davis Medical Center, University of California at Davis, Davis, 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