This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objective of this study is to determine the role of caveolae in airway remodeling in asthma. This chronic inflammatory disease of the airways affects an estimated 15 million people in the United States and 100-150 million people worldwide. Among this population at risk, a subset of subjects will develop irreversible remodeling and airway obstruction. Airway remodeling is characterized by an abnormally large number of myofibroblasts in the subepithelial basement membrane associated with significantly increased deposition of connective tissue proteins leading to a thickening of the lamina reticularis. Interleukin 4 (IL-4), a Th2 cytokine important in the control of allergic response, has also been proposed as an effector influencing airway remodeling. We have recently demonstrated that IL-4 regulates the expression of caveolin-1 (cav-1). Cav-1, main structural and functional protein of caveolae, notably regulates transforming growth factor (TGF)-beta activity by dampening its transduction signal process initiated by the TGF-beta receptor complex. TGF-beta1 is a pivotal pro-fibrotic cytokine in asthma and fibrosis. Our goal, therefore, is to demonstrate that Th2 cytokines, and more specifically IL-4, mediate caveolae deficiency by regulating cav-1 gene transcription in fibroblasts resulting in enhanced TGF-beta responses in airway remodeling. We will: 1) Evaluate the hypothesis that the reduced expression of cav1 is associated with the expression of inflammatory markers, more specifically IL-4 and TGF-beta, and the development of airway remodeling in allergen challenged mice. 2) Investigate the hypothesis that among the Th2 cytokines expressed in asthma, IL-4 regulates caveolin-1 expression and caveolae formation;3) To test the hypothesis that the reduced expression of caveolin-1 protein enhances TGF-beta effects.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Exploratory Grants (P20)
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Special Emphasis Panel (ZRR1-RI-7 (01))
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University of Hawaii
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Kaholokula, Joseph Keawe'aimoku; Antonio, Mapuana C K; Ing, Claire K Townsend et al. (2017) The effects of perceived racism on psychological distress mediated by venting and disengagement coping in Native Hawaiians. BMC Psychol 5:2
Yu, Xufen; Zhang, Mingming; Annamalai, Thirunavukkarasu et al. (2017) Synthesis, evaluation, and CoMFA study of fluoroquinophenoxazine derivatives as bacterial topoisomerase IA inhibitors. Eur J Med Chem 125:515-527
Jarvi, Susan I; Bianchi, Kiara R; Farias, Margaret Em et al. (2016) Characterization of class II ? chain major histocompatibility complex genes in a family of Hawaiian honeycreepers: 'amakihi (Hemignathus virens). Immunogenetics 68:461-475
Sun, Zuyue; Schriewer, Jill; Tang, Mingxin et al. (2016) The TGF-? pathway mediates doxorubicin effects on cardiac endothelial cells. J Mol Cell Cardiol 90:129-38
Youn, Ui Joung; Sripisut, Tawanun; Park, Eun-Jung et al. (2015) Determination of the absolute configuration of chaetoviridins and other bioactive azaphilones from the endophytic fungus Chaetomium globosum. Bioorg Med Chem Lett 25:4719-23
Miklossy, Gabriella; Youn, Ui Joung; Yue, Peibin et al. (2015) Hirsutinolide Series Inhibit Stat3 Activity, Alter GCN1, MAP1B, Hsp105, G6PD, Vimentin, TrxR1, and Importin ?-2 Expression, and Induce Antitumor Effects against Human Glioma. J Med Chem 58:7734-48
Panee, Jun (2015) Potential Medicinal Application and Toxicity Evaluation of Extracts from Bamboo Plants. J Med Plant Res 9:681-692
Panee, Jun; Pang, Xiaosha; Munsaka, Sody et al. (2015) Independent and co-morbid HIV infection and Meth use disorders on oxidative stress markers in the cerebrospinal fluid and depressive symptoms. J Neuroimmune Pharmacol 10:111-21
Rueli, Rachel H L H; Parubrub, Arlene C; Dewing, Andrea S T et al. (2015) Increased selenoprotein P in choroid plexus and cerebrospinal fluid in Alzheimer's disease brain. J Alzheimers Dis 44:379-83
Hamad, Mazen Lee; Engen, William; Morris, Kenneth R (2015) Impact of hydration state and molecular oxygen on the chemical stability of levothyroxine sodium. Pharm Dev Technol 20:314-9

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