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Although murine X-linked muscular dystrophy (mdx) and Duchenne muscular dystrophy (DMD) are genetically homologous and both characterized by a complete absence of dystrophin, the limb muscles of adult mdx mice suffer neither the detectable weakness nor the progressive degeneration that are features of DMD. Here we show that the mdx mouse diaphragm exhibits(More)
Recently, bitter taste receptors (TAS2Rs) were found in the lung and act to relax airway smooth muscle (ASM) via intracellular Ca(2+) concentration signaling generated from restricted phospholipase C activation. As potential therapy, TAS2R agonists could be add-on treatment when patients fail to achieve adequate bronchodilation with chronic β-agonists. The(More)
We measured the time course and heterogeneity of responses to contractile and relaxing agonists in individual human airway smooth muscle (HASM) cells in culture. To this end, we developed a microrheometer based on magnetic twisting cytometry adapted with a novel optical detection system. Ferromagnetic beads (4.5 microm) coated with Arg-Gly-Asp peptide were(More)
A new paradigm for asthma pathogenesis is presented in which exaggerated inflammation and remodeling in the airways are a consequence of abnormal injury and repair responses arising from a subject's susceptibility to components of the inhaled environment. An epithelial-mesenchymal trophic unit becomes activated to drive pathologic remodeling and smooth(More)
We examined the influence of two common polymorphic forms of the beta(2)-adrenergic receptor (beta(2)AR): the Gly16 and Glu27 alleles, on acute and long-term beta(2)AR desensitization in human airway smooth muscle (HASM) cells. In cells from 15 individuals, considered without respect to genotype, pretreatment with Isoproterenol (ISO) at 10(-7) M for 1 h or(More)
Despite recent studies depicting the capacity of G protein-coupled receptors (GPCRs) to activate mitogenic signaling pathways more commonly associated with receptor tyrosine kinases (RTKs), little is known regarding the interactive effects of GPCR and RTK activation on cell growth and signal transduction. Such interactions likely mediate the physiologic(More)
A-kinase anchoring proteins (AKAPs) have emerged as important regulatory molecules that can compartmentalize cAMP signaling transduced by β2-adrenergic receptors (β(2)ARs); such compartmentalization ensures speed and fidelity of cAMP signaling and effects on cell function. This study aimed to assess the role of AKAPs in regulating global and(More)
The cysteinyl leukotrienes (CysLTs) mimic many of the features of asthma and are implicated in its pathophysiology. Little, however, is known about the effects of the CysLTs on airways remodeling. In this study the effects of leukotriene D4 (LTD4) on human airway smooth muscle (HASM) cell proliferation and expression of extracellular matrix proteins were(More)
Airway smooth muscle (ASM) plays a central role in regulating bronchomotor tone in patients with asthma. New evidence, however, suggests that ASM may also orchestrate and perpetuate airway inflammation by promoting the recruitment, activation, and trafficking of inflammatory cells in the airways. This review addresses the immunomodulatory function of ASM(More)
Asthma is a disease of airway inflammation and hyperreactivity that is associated with a lymphocytic infiltrate in the bronchial submucosa. The interactions between infiltrating T lymphocytes with cellular and extracellular matrix components of the airway and the consequences of these interactions have not been defined. We demonstrate the constitutive(More)