title: Role of the adiponectin binding protein, T-cadherin (Cdh13), in allergic airways responses in mice.
abstract: Adiponectin is an adipose derived hormone that declines in obesity. We have previously shown that exogenous administration of adiponectin reduces allergic airways responses in mice. T-cadherin (T-cad; Cdh13) is a binding protein for the high molecular weight isoforms of adiponectin. To determine whether the beneficial effects of adiponectin on allergic airways responses require T-cad, we sensitized wildtype (WT), T-cadherin deficient (T-cad(-/-)) and adiponectin and T-cad bideficient mice to ovalbumin (OVA) and challenged the mice with aerosolized OVA or PBS. Compared to WT, T-cad(-/-) mice were protected against OVA-induced airway hyperresponsiveness, increases in BAL inflammatory cells, and induction of IL-13, IL-17, and eotaxin expression. Histological analysis of the lungs of OVA-challenged T-cad(-/-) versus WT mice indicated reduced inflammation around the airways, and reduced mucous cell hyperplasia. Combined adiponectin and T-cad deficiency reversed the effects of T-cad deficiency alone, indicating that the observed effects of T-cad deficiency require adiponectin. Compared to WT, serum adiponectin was markedly increased in T-cad(-/-) mice, likely because adiponectin that is normally sequestered by endothelial T-cad remains free in the circulation. In conclusion, T-cad does not mediate the protective effects of adiponectin. Instead, mice lacking T-cad have reduced allergic airways disease, likely because elevated serum adiponectin levels act on other adiponectin signaling pathways.
authors: Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors: Alison S
authors: AS
authors: Williams
authors: David I
authors: DI
authors: Kasahara
authors: Norah G
authors: NG
authors: Verbout
authors: Alexey V
authors: AV
authors: Fedulov
authors: Ming
authors: M
authors: Zhu
authors: Huiqing
authors: H
authors: Si
authors: Allison P
authors: AP
authors: Wurmbrand
authors: Christopher
authors: C
authors: Hug
authors: Barbara
authors: B
authors: Ranscht
authors: Stephanie A
authors: SA
authors: Shore
mesh_terms: D052242:Adiponectin / Q000097:blood / Q000378:metabolism*; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000378:metabolism; D018893:Bronchoalveolar Lavage; D015820:Cadherins / Q000378:metabolism / Q000502:physiology*; D003433:Crosses, Genetic; D007249:Inflammation; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000494:pharmacology; D011485:Protein Binding; D015398:Signal Transduction
chemical_list: D052242:Adiponectin; D015820:Cadherins; C099972:H-cadherin; D010047:Ovalbumin