Kasahara, DavidWilliams, Alison S.Benedito, Leandro A.Ranscht, BarbaraKobzik, LesterHug, ChristopherShore, Stephanie2014-02-132013Kasahara, David I., Alison S. Williams, Leandro A. Benedito, Barbara Ranscht, Lester Kobzik, Christopher Hug, and Stephanie A. Shore. 2013. “Role of the Adiponectin Binding Protein, T-Cadherin (cdh13), in Pulmonary Responses to Subacute Ozone.” PLoS ONE 8 (6): e65829. doi:10.1371/journal.pone.0065829. http://dx.doi.org/10.1371/journal.pone.0065829.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:11708575Adiponectin, an adipose derived hormone with pleiotropic functions, binds to several proteins, including T-cadherin. We have previously reported that adiponectin deficient (Adipo−/−) mice have increased IL-17A-dependent neutrophil accumulation in their lungs after subacute exposure to ozone (0.3 ppm for 72 hrs). The purpose of this study was to determine whether this anti-inflammatory effect of adiponectin required adiponectin binding to T-cadherin. Wildtype, Adipo−/−, T-cadherin deficient (T-cad−/−), and bideficient (Adipo−/−/T-cad−/−) mice were exposed to subacute ozone or air. Compared to wildtype mice, ozone-induced increases in pulmonary IL-17A mRNA expression were augmented in T-cad−/− and Adipo−/− mice. Compared to T-cad−/− mice, there was no further increase in IL-17A in Adipo−/−/T-cad−/− mice, indicating that adiponectin binding to T-cadherin is required for suppression of ozone-induced IL-17A expression. Similar results were obtained for pulmonary mRNA expression of saa3, an acute phase protein capable of inducing IL-17A expression. Comparison of lung histological sections across genotypes also indicated that adiponectin attenuation of ozone-induced inflammatory lesions at bronchiolar branch points required T-cadherin. BAL neutrophils and G-CSF were augmented in T-cad−/− mice and further augmented in Adipo−/−/T-cad−/− mice. Taken together with previous observations indicating that augmentation of these moieties in ozone exposed Adipo−/− mice is partially IL-17A dependent, the results indicate that effects of T-cadherin deficiency on BAL neutrophils and G-CSF are likely secondary to changes in IL-17A, but that adiponectin also acts via T-cadherin independent pathways. Our results indicate that T-cadherin is required for the ability of adiponectin to suppress some but not all aspects of ozone-induced pulmonary inflammation.en-USBiologyHistologyImmunologyImmune SystemCytokinesImmunityInflammationImmune ResponseModel OrganismsAnimal ModelsMouseMolecular Cell BiologyGene ExpressionEarth SciencesAtmospheric ScienceAtmospheric ChemistryOzoneMathematicsStatisticsBiostatisticsMedicineAnatomy and PhysiologyRespiratory SystemClinical ImmunologyMetabolic DisordersPulmonologyAsthmaEnvironmental and Occupational Lung DiseasesJournal Article2014-02-1310.1371/journal.pone.0065829