title: Tiotropium bromide suppresses smoke inhalation and burn injury-induced ERK 1/2 and SMAD 2/3 signaling in sheep bronchial submucosal glands.
abstract: The effects of tiotropium bromide on ERK 1/2, SMAD 2/3 and NFκB signaling in bronchial submucosal gland (SMG) cells of sheep after smoke inhalation and burn injury (S + B) were studied. We hypothesized that tiotropium would modify intracellular signaling processes within SMG cells after injury. Bronchial tissues were obtained from uninjured (sham, n = 6), S + B injured sheep 48 h after injury (n = 6), and injured sheep nebulized with tiotropium (n = 6). The percentage (mean ± SD) of cells showing nuclear localization of phosphorylated ERK 1/2, pSMAD 2/3, and NFκB (p65) was determined by immunohistochemistry. Nuclear pERK 1/2 staining was increased in injured animals as compared to sham, (66 ± 20 versus 14 ± 9), p = 0.0022, as was nuclear pSMAD, 84 ± 10 versus 20 ± 10, p = 0.0022. There was a significant decrease in pERK 1/2 labeling in the tiotropium group compared to the injured group (31 ± 20 versus 66 ± 20, p = 0.013), and also a decrease in pSMAD labeling, 62 ± 17 versus 84 ± 10, p = 0.04. A significant increase for NFκB (p65) was noted in injured animals as compared to sham (73 ± 16 versus 7 ± 6, p = 0.0022). Tiotropium-treated animals showed decreased p65 labeling as compared to injured (35 ± 17 versus 74 ± 16, p = 0.02). The decrease in nuclear expression of pERK, pSMAD and NFκB molecules in SMG cells with tiotropium treatment is suggestive that their activation after injury is mediated in part through muscarinic receptors.
authors.affiliation: Shriners Hospital for Children and the University of Texas Medical Branch , Galveston, TX , USA.
authors.forename: Sam
authors.initials: S
authors.lastname: Jacob
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Sven
authors.initials: S
authors.lastname: Asmussen
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
authors.forename: David N
authors.initials: DN
authors.lastname: Herndon
authors.forename: Perenlei
authors.initials: P
authors.lastname: Enkhbaatar
authors.forename: Hal K
authors.initials: HK
authors.lastname: Hawkins
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cox
mesh_terms: D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001993:Bronchodilator Agents / Q000494:pharmacology*; D002056:Burns / Q000517:prevention & control*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D012602:Scopolamine Derivatives / Q000494:pharmacology*; D012756:Sheep; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism*; D015208:Smoke Inhalation Injury / Q000517:prevention & control*; D000069447:Tiotropium Bromide
chemical_list: D001993:Bronchodilator Agents; D012602:Scopolamine Derivatives; D051899:Smad2 Protein; D051900:Smad3 Protein; D000069447:Tiotropium Bromide