{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T16:19:54Z","timestamp":1782922794342,"version":"3.54.5"},"reference-count":45,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:p> Diseases such as asthma are characterized by airway hyperresponsiveness. Enhanced airway smooth muscle (ASM) intracellular Ca<jats:sup>2+<\/jats:sup> ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) response to agonist stimulation leading to increased airway constriction has been suggested to contribute to airway hyperresponsiveness. Caveolae are flask-shaped plasma membrane invaginations that express the scaffolding protein caveolin and contain multiple proteins important in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> signaling (e.g., agonist receptors, ion channels). We recently demonstrated that caveolae and caveolin-1 are important in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> regulation in human ASM. Proinflammatory cytokines such as tumor necrosis factor (TNF)-\u03b1 and interleukin (IL)-13 modulate [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> in ASM. We hypothesized that cytokine upregulation of caveolar signaling in ASM contributes to enhanced agonist-induced [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> in inflammation. Enzymatically dissociated human ASM cells were exposed to medium (control), 20 ng\/ml TNF-\u03b1, or 50 ng\/ml IL-13 for 24 h. Caveolae-enriched membrane fractions displayed substantial increase in caveolin-1 and -2 expressions by TNF-\u03b1 and IL-13. Transfection with caveolin-1-mRed DNA substantially accelerated and increased plasma membrane caveolin-1 expression by TNF-\u03b1 and to a lesser extent by IL-13. Caveolin-1 enhancement was inhibited by nuclear factor-\u03baB and mitogen-activated protein kinase inhibitors. In fura 2-loaded ASM cells, [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> responses to 1 \u03bcM ACh, 10 \u03bcM histamine, or 10 nM bradykinin were all exaggerated by TNF-\u03b1 as well as IL-13 exposure. However, disruption of caveolae using caveolin-1 suppression via small-interfering RNA resulted in significant blunting of agonist-induced [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> responses of vehicle and TNF-\u03b1-exposed cells. These functional data were correlated to the presence of TNFR<jats:sub>1<\/jats:sub> receptor (but not the IL-4\/IL-13 receptor) within caveolae. Overall, these results indicate that caveolin-1 plays an important role in airway inflammation by modulating the effect of specific cytokines on [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. <\/jats:p>","DOI":"10.1152\/ajplung.00019.2011","type":"journal-article","created":{"date-parts":[[2011,7,30]],"date-time":"2011-07-30T03:00:29Z","timestamp":1311994829000},"page":"L607-L614","source":"Crossref","is-referenced-by-count":32,"title":["Caveolin-1 in cytokine-induced enhancement of intracellular Ca<sup>2+<\/sup> in human airway smooth muscle"],"prefix":"10.1152","volume":"301","author":[{"given":"Venkatachalem","family":"Sathish","sequence":"first","affiliation":[{"name":"Departments of 1Anesthesiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amard J.","family":"Abcejo","sequence":"additional","affiliation":[{"name":"Departments of 1Anesthesiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Kay","family":"VanOosten","sequence":"additional","affiliation":[{"name":"Departments of 1Anesthesiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Departments of 1Anesthesiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. 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