title: Resistin deficiency in mice has no effect on pulmonary responses induced by acute ozone exposure.
abstract: Acute exposure to ozone (O3), an air pollutant, causes pulmonary inflammation, airway epithelial desquamation, and airway hyperresponsiveness (AHR). Pro-inflammatory cytokines-including IL-6 and ligands of chemokine (C-X-C motif) receptor 2 [keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-2], TNF receptor 1 and 2 (TNF), and type I IL-1 receptor (IL-1α and IL-1β)-promote these sequelae. Human resistin, a pleiotropic hormone and cytokine, induces expression of IL-1α, IL-1β, IL-6, IL-8 (the human ortholog of murine KC and MIP-2), and TNF. Functional differences exist between human and murine resistin; yet given the aforementioned observations, we hypothesized that murine resistin promotes O3-induced lung pathology by inducing expression of the same inflammatory cytokines as human resistin. Consequently, we examined indexes of O3-induced lung pathology in wild-type and resistin-deficient mice following acute exposure to either filtered room air or O3. In wild-type mice, O3 increased bronchoalveolar lavage fluid (BALF) resistin. Furthermore, O3 increased lung tissue or BALF IL-1α, IL-6, KC, TNF, macrophages, neutrophils, and epithelial cells in wild-type and resistin-deficient mice. With the exception of KC, which was significantly greater in resistin-deficient compared with wild-type mice, no genotype-related differences in the other indexes existed following O3 exposure. O3 caused AHR to acetyl-β-methylcholine chloride (methacholine) in wild-type and resistin-deficient mice. However, genotype-related differences in airway responsiveness to methacholine were nonexistent subsequent to O3 exposure. Taken together, these data demonstrate that murine resistin is increased in the lungs of wild-type mice following acute O3 exposure but does not promote O3-induced lung pathology.
authors.affiliation: Division of Critical Care Medicine, Department of Pediatrics, The University of Texas Medical School at Houston, Houston, Texas;
authors.forename: Shehla S
authors.initials: SS
authors.lastname: Razvi
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina;
authors.forename: Jeremy B
authors.initials: JB
authors.lastname: Richards
authors.affiliation: Division of Critical Care Medicine, Department of Pediatrics, The University of Texas Medical School at Houston, Houston, Texas;
authors.forename: Farhan
authors.initials: F
authors.lastname: Malik
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York;
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Cromar
authors.affiliation: Comparative Pathology Laboratory, Center for Comparative Medicine, Baylor College of Medicine, Houston, Texas;
authors.forename: Roger E
authors.initials: RE
authors.lastname: Price
authors.affiliation: Division of Nephrology, Department of Pediatrics, The University of Texas Medical School at Houston, Houston, Texas;
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Bell
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Texas Medical School at Houston, Houston, Texas;
authors.forename: Tingting
authors.initials: T
authors.lastname: Weng
authors.affiliation: Division of Pulmonary Medicine, Department of Pediatrics, The University of Texas Medical School at Houston, Houston, Texas;
authors.forename: Constance L
authors.initials: CL
authors.lastname: Atkins
authors.affiliation: Pediatric Pulmonary Section, Department of Pediatrics, Baylor College of Medicine, Houston, Texas;
authors.forename: Chantal Y
authors.initials: CY
authors.lastname: Spencer
authors.affiliation: Pediatric Research Center, Department of Pediatrics, The University of Texas Medical School at Houston, Houston, Texas;
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Cockerill
authors.affiliation: Pediatric Research Center, Department of Pediatrics, The University of Texas Medical School at Houston, Houston, Texas;
authors.forename: Amy L
authors.initials: AL
authors.lastname: Alexander
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Texas Medical School at Houston, Houston, Texas;
authors.forename: Michael R
authors.initials: MR
authors.lastname: Blackburn
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Texas Medical School at Houston, Houston, Texas; Pediatric Research Center, Department of Pediatrics, The University of Texas Medical School at Houston, Houston, Texas; Division of Neonatal-Perinatal Medicine, Department of Pediatrics, The University of Texas Medical School at Houston, Houston, Texas; and.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Alcorn
authors.affiliation: Division of Critical Care Medicine, Department of Pediatrics, The University of Texas Medical School at Houston, Houston, Texas;
authors.forename: Ikram U
authors.initials: IU
authors.lastname: Haque
authors.affiliation: Division of Critical Care Medicine, Department of Pediatrics, The University of Texas Medical School at Houston, Houston, Texas; Pediatric Research Center, Department of Pediatrics, The University of Texas Medical School at Houston, Houston, Texas; Department of Integrative Biology and Pharmacology, The University of Texas Medical School at Houston, Houston, Texas Richard.A.Johnston@uth.tmc.edu.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Johnston
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D005260:Female; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010126:Ozone / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism*; D052243:Resistin / Q000097:blood / Q000235:genetics*
chemical_list: D000393:Air Pollutants; D016085:Bronchoconstrictor Agents; D052243:Resistin; C499623:Retn protein, mouse; D016210:Methacholine Chloride; D010126:Ozone
keywords: TNF; airway responsiveness; inflammation; keratinocyte chemoattractant; methacholine