We examined the effect of transforming growth factor-beta 1 (TGF-beta 1) on the in vitro motility of interleukin-2-activated natural killer (IANK) cells. Low doses of TGF-beta 1 (0.01 or 0.1 ng/ml) are chemotactic for these cells as determined by modified Boyden chamber assay. IANK cells bind biotinylated TGF-beta suggesting that they express receptors for this cytokine. TGF-beta 1-induced IANK cell chemotaxis was inhibited by protein kinase C inhibitors, such as staurosporine and H7. The role of calcium mobilization in TGF-beta 1 activity was also examined; the inhibitor of intracellular Ca2+, TMB-8, inhibited TGF-beta 1-induced IANK cell chemotaxis. Supporting the role for Ca2+ mobilization is the ability of low doses of TGF-beta 1 to induce the recruitment of intracellular Ca2+ as determined by a fura-2-AM-loaded-cell assay.
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