PGE2 Desensitizes β-Agonist Effect on Human Lung Fibroblast-Mediated Collagen Gel Contraction through Upregulating PDE4
Figure 3
Indomethacin potentiates salmeterol but not cilomilast. Confluent HFL-1 cells were pretreated with SF-DMEM with or without 10−6 M indomethacin for 24 hrs. The next day, cells were cast into collagen gels as described in Section 2. (a) Indomethacin pretreatment potentiated the salmeterol effect on fibroblast-mediated collagen gel contraction. Gels were released into SF-DMEM supplemented with varying concentrations of salmeterol as indicated. Vertical axis: gel size on day 2 (%); horizontal axis: salmeterol concentrations (M). Square: cells were cultured in SF-DMEM for 24 hrs prior to being cast into collagen gels; triangle: cells were pretreated with 10−6 M indomethacin for 24 hrs prior to being cast into collagen gels. * compared to control at each time point. (b) Indomethacin pretreatment did not affect the cilomilast effect. Gels were released into SF-DMEM containing varying concentrations of cilomilast as indicated. Vertical axis: gel size on day 2 (%); horizontal axis: cilomilast concentrations (M). Square: cells were cultured in SF-DMEM for 24 hrs prior to being cast into collagen gels; triangle: cells were pretreated with 1 μM indomethacin for 24 hrs prior to being cast into collagen gels. (c) Indomethacin further potentiated the synergistic effect of salmeterol and cilomilast added together on fibroblast-mediated collagen gel contraction. Gels were released into SF-DMEM with or without salmeterol and/or cilomilast as indicated. Vertical axis: gel size on day 2 (%); horizontal axis: reagents in the medium in which gels were floated. Open bars: cells were cultured in SF-DMEM for 24 hrs prior to being cast into collagen gels; hatched bars: cells were pretreated with 10−6 M indomethacin for 24 hrs prior to being cast into collagen gels. *; **.
