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• W22240057 endingPage "L1028" @default.
• W22240057 startingPage "L1020" @default.
• W22240057 abstract "We have previously shown that tumor necrosis factor (TNF)-α, a cytokine involved in asthma, enhances Ca 2+ responsiveness to bronchoconstrictor agents in cultured human airway smooth muscle (ASM) cells. In the present study, we investigated the potential mechanism(s) by which TNF-α modulates ASM cell responsiveness to such agents. In human ASM cells loaded with fura 2, TNF-α and interleukin (IL)-1β significantly enhanced thrombin- and bradykinin-evoked elevations of intracellular Ca 2+ . In TNF-α-treated cells, Ca 2+ responses to thrombin and bradykinin were 350 ± 14 and 573 ± 93 nM vs. 130 ± 17 and 247 ± 48 nM in nontreated cells, respectively ( P < 0.0001). In IL-1β-treated cells, the Ca 2+ response to bradykinin was 350 ± 21 vs. 127 ± 12 nM in nontreated cells ( P < 0.0001). The time course for TNF-α potentiation of agonist-induced Ca 2+ responses requires a minimum of 6 h and was maximum after 12 h of incubation. In addition, cycloheximide, a protein synthesis inhibitor, completely blocked the potentiating effect of TNF-α on Ca 2+ signals. We also found that TNF-α significantly enhanced increases in phosphoinositide (PI) accumulation induced by bradykinin. The percentage of change in PI accumulation over control was 115 ± 8 to 210 ± 15% in control cells vs. 128 ± 10 to 437 ± 92% in TNF-α-treated cells for 3 × 10 −9 to 3 × 10 −6 M bradykinin. The PI turnover to 10 mM NaF, a direct activator of G proteins, was also found to be enhanced by TNF-α. The percentage of change in PI accumulation over control increased from 280 ± 35% in control cells to 437 ± 92% in TNF-α-treated cells. Taken together, these results show that TNF-α can potently regulate G protein-mediated signal transduction in ASM cells by activating pathways dependent on protein synthesis. Our study demonstrates one potential mechanism underlying the enhanced Ca 2+ response to bronchoconstrictor agents induced by cytokines in human ASM cells." @default.
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• W22240057 date "1997-11-01" @default.
• W22240057 modified "2023-09-26" @default.
• W22240057 title "Mechanisms underlying TNF-α effects on agonist-mediated calcium homeostasis in human airway smooth muscle cells" @default.
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• W22240057 doi "https://doi.org/10.1152/ajplung.1997.273.5.l1020" @default.
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