title: Adiponectin and functional adiponectin receptor 1 are expressed by airway epithelial cells in chronic obstructive pulmonary disease.
abstract: We screened bronchoalveolar lavage (BAL) fluids from COPD-E (chronic obstructive pulmonary disease-Emphysema) and control subjects using a 120 Ab cytokine array and demonstrated that adiponectin was highly expressed in BAL in COPD-E. An adiponectin ELISA confirmed that adiponectin was highly expressed in BAL in COPD-E compared with smokers and healthy control subjects. Immunohistochemistry studies of lung sections from subjects with COPD-E demonstrated that airway epithelial cells expressed significant levels of adiponectin and adiponectin receptor (AdipoR) 1 but not AdipoR2. In vitro studies with purified populations of human lung A549 epithelial cells demonstrated that they expressed both adiponectin and AdipoR1 (but not AdipoR2) as assessed by RT-PCR, Western blot, and immunohistochemistry. Lung A549 epithelial AdipoR1were functional as incubation with adiponectin induced release of IL-8, which was inhibited by small interfering RNA to AdipoR1. Using a mouse model of COPD, tobacco smoke exposure induced both evidence of COPD as well as increased levels of adiponectin in BAL fluid and increased adiponectin expression by airway epithelial cells. As adiponectin expression in adipocytes is dependent upon NF-kappaB we determined levels of adiponectin in tobacco smoke exposed CC10-Cre(tg)/Ikkbeta(Delta/Delta) mice (deficient in the ability to activate NF-kappaB in airway epithelium). These studies demonstrated that CC10-Cre(tg)/Ikkbeta(Delta/Delta) and wild-type mice had similar levels of BAL adiponectin and airway epithelial adiponectin immunostaining. Overall, these studies demonstrate the novel observation that adiponectin and functional AdipoR1are expressed by lung epithelial cells, suggesting a potential autocrine and/or paracrine pathway for adiponectin to activate epithelial cells in COPD-E.
authors.affiliation: Department of Medicine, University of California San Diego, San Diego, CA 92093, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Miller
authors.forename: Jae Youn
authors.initials: JY
authors.lastname: Cho
authors.forename: Alexa
authors.initials: A
authors.lastname: Pham
authors.forename: Joe
authors.initials: J
authors.lastname: Ramsdell
authors.forename: David H
authors.initials: DH
authors.lastname: Broide
mesh_terms: D052242:Adiponectin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000502:physiology; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011656:Pulmonary Emphysema / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D054419:Receptors, Adiponectin / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
chemical_list: C499918:ADIPOQ protein, human; C475418:ADIPOR1 protein, human; D052242:Adiponectin; C499919:Adipoq protein, mouse; D016209:Interleukin-8; D016328:NF-kappa B; D054419:Receptors, Adiponectin; C475419:adiponectin receptor 1, mouse