Mechanisms of asthma and allergic inflammationTGF-β differentially regulates TH2 cytokine-induced eotaxin and eotaxin-3 release by human airway smooth muscle cells
Section snippets
HASM culture
HASMs from 2 donors were purchased from Stratagene (La Jolla, Calif). Cells were characterized and stained positive for α-smooth muscle actin. Cells were cultured in Dulbecco modified Eagle medium/nutrient mixture F12 (1:1; Invitrogen, Carlsbad, Calif) containing 25 mmol/L HEPES (Invitrogen), 10% (vol/vol) FCS (Invitrogen) supplemented with 2.5 mmol/L l-glutamine (Cambrex, East Rutherford, NJ), 1% (vol/vol) nonessential amino acids (Invitrogen), 50 U/mL penicillin, and 50 μg/mL streptomycin
Cytokine-induced eotaxin and eotaxin-3 release
To study the effect of TH2 cytokines on the release of eotaxins by HASMs, serum-starved confluent monolayers were incubated with IL-4, IL-13, and IL-9 in serum-free medium. The TH2 cytokines IL-4 and IL-13 induced eotaxin and eotaxin-3 release by HASMs in a dose-dependent manner (Fig 1, A and B). IL-4 induced eotaxin release at low concentrations, whereas IL-13 was less potent in inducing eotaxin release. Eotaxin-3 release, however, was induced at low concentrations of both IL-4 and IL-13.
Discussion
In this study we have shown that HASMs produce eotaxin and eotaxin-3 upon stimulation with the TH2 cytokines IL-4 and IL-13. HASMs did not release eotaxin-2 protein upon stimulation with the TH2 cytokines IL-4 and IL-13. A low concentration (0.5 ng/mL) of TGF-β increased IL-4–induced and IL-13–induced eotaxin release, whereas it decreased the release of eotaxin-3. At the same concentration, TGF-β alone altered neither eotaxin nor eotaxin-3 release.
We have shown for the first time that IL-4 and
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Funded by The Netherlands Asthma Foundation (grant 00.17) and AstraZeneca (Lund, Sweden).