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The effect of cytokines on the taurine uptake by human intestinal epithelial Caco-2 cells was investigated. Among the various cytokines tested, tumor necrosis factor α (TNF-α) markedly increased the taurine uptake by Caco-2 cells, resulting in an increase in the intracellular taurine level. TNF-α did not induce up-regulation of the taurine uptake in hepatic HepG2, renal human embryo kidney 293, and macrophage-like THP-1 cells. The uptake of glycine, L-leucine, and L-glutamic acid by Caco-2 cells was not affected by TNF-α. A kinetic analysis of the taurine uptake by TNF-α-treated Caco-2 cells suggests that this up-regulation was associated with both an increase in the amount of the taurine transporter (TAUT) and an increase in its affinity. TNF-α-treated cells showed a higher mRNA level of the TAUT than did the control cells. [Copyright &y& Elsevier]

Hepatocellular lineage cell lines (two hepatoma and Chang liver cell lines) were found to produce interleukin-6 (IL-6). As the human hepatoma cell line, HCC-M expresses mRNA for both IL-6 and IL-6 receptor, we examined the possibility that IL-6 acted as an autocrine growth factor for HCC-M cells using two IL-6 antisense oligonucleotides (AS-1 and AS-2 oligomers) which were synthesized from different regions of an IL-6 cDNA clone. Both IL-6 antisense oligonucleotides inhibited the growth of HCC-M cells within 48 h (% inhibition by AS-1 and AS-2 oligomers was 53 and 21%, respectively). Although inhibition of HCC-M cell growth induced by AS-2 oligomer was restored by addition of exogenous recombinant IL-6 (rIL-6), the inhibition of growth induced by AS-1 oligomer was not fully restored by exogenous rIL-6, implicating the involvement of a nonantisense mechanism associated with four contiguous guanosine residues in this sequence. The inhibitory effect of AS-2 oligomer was attenuated after 72 h (% inhibition was 8%), whereas the AS-1 oligomer-induced inhibition of growth was sustained beyond 72 h (% inhibition was 38–39%). Therefore, these dual-function oligonucleotides that act via both an antisense and nonantisense mechanism may be of potential therapeutic value against hepatoma. [ABSTRACT FROM AUTHOR]