{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:20:50Z","timestamp":1790626850721,"version":"4.1.0"},"reference-count":59,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2004,12]]},"abstract":"<jats:p>Chemokine synthesis by airway smooth muscle cells (ASMC) may be an important process underlying inflammatory cell recruitment in airway inflammatory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Fractalkine (FKN) is a recently described CX<jats:sub>3<\/jats:sub>C chemokine that has dual functions, serving as both a cell adhesion molecule and a chemoattractant for monocytes and T cells, expressing its unique receptor, CX<jats:sub>3<\/jats:sub>CR1. We investigated FKN expression by human ASMC in response to the proinflammatory cytokines IL-1\u03b2, TNF-\u03b1, and IFN-\u03b3, the T helper 2-type cytokines IL-4, IL-10, and IL-13, and the fibrogenic cytokine transforming growth factor (TGF)-\u03b2. Neither of these cytokines alone had any significant effect on ASMC FKN production. Combined stimulation with IFN-\u03b3 and TNF-\u03b1 induced FKN mRNA and protein expression in a time- and concentration-dependent manner. TGF-\u03b2 had a significant inhibitory effect on cytokine-induced FKN mRNA and protein expression. Dexamethasone (10<jats:sup>\u22128<\/jats:sup>\u201310<jats:sup>\u22126<\/jats:sup>M) significantly upregulated cytokine-induced FKN mRNA and protein expression. Finally, we used selective inhibitors of the mitogen-activated protein kinases c-Jun NH<jats:sub>2<\/jats:sub>-terminal kinase (JNK) (SP-610025), p38 (SB-203580), and extracellular signal-regulated kinase (PD-98095) to investigate their role in FKN production. SP-610025 (25 \u03bcM) and SB-203580 (20 \u03bcM), but not PD-98095, significantly attenuated cytokine-induced FKN protein synthesis. IFN-\u03b3- and TNF-\u03b1-induced JNK phosphorylation remained unaltered in the presence of TGF-\u03b2 but was inhibited by dexamethasone, indicating that JNK is not involved in TGF-\u03b2- or dexamethasone-mediated regulation of FKN production. In summary, FKN production by human ASMC in vitro is regulated by inflammatory and anti-inflammatory factors.<\/jats:p>","DOI":"10.1152\/ajplung.00014.2004","type":"journal-article","created":{"date-parts":[[2004,8,21]],"date-time":"2004-08-21T01:28:13Z","timestamp":1093051693000},"page":"L1230-L1240","source":"Crossref","is-referenced-by-count":76,"title":["Fractalkine\/CX<sub>3<\/sub>CL1 production by human airway smooth muscle cells: induction by IFN-\u03b3 and TNF-\u03b1 and regulation by TGF-\u03b2 and corticosteroids"],"prefix":"10.1152","volume":"287","author":[{"given":"Maria B.","family":"Sukkar","sequence":"first","affiliation":[{"name":"Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, SW3 6LY, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razao","family":"Issa","sequence":"additional","affiliation":[{"name":"Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, SW3 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