The role of myo-inositol in the regulation of taurine transport in activated murine macrophage cell line, RAW 264.7, was studied. Challenge of RAW 264.7 murine macrophages for 24 hr with phorbol ester 12-myristate 13-acetate (PMA) (10 ng/ml), a PKC activator, resulted in a 62% decrease in taurine transport activity. Among the various monosaccharides (1 mM) tested in the presence of PMA, myo-inositol was most effective in restoring the PMA-induced down-regulation of taurine transport in murine macrophages (82% increase compared to the value for cells treated with PMA Alone, p < 0.01). The protective role of myo-inositol against stress-induced down-regulation of taurine transport by macrophages was further investigated in conditions mimicking bacterial infection, inflammation, and immune-suppressed circumstances. A challenge of murine macrophages with lipopolysaccharide (LPS) (0.1 and 10 μg/ml) resulted in a 60% decrease in taurine transport activity compared to the value for untreated control cells (p < 0.01). When cells were co-treated with myo-inositol (100 nM ∼ 10 mM) in the presence of LPS for 24 hrs, taurine transport activity increased in a dose-dependent manner compared to the value for cells treated with LPS only. Taurine transport activity in cells treated with LPS (10 μg/ml) plus interferon-gamma (IFN-γ) (150 unit/ml) for 24 hrs was 13% of the value for untreated control cells (p < 0.01). Again, this inflammation-induced down-regulation of taurine transport activity was completely antagonized with co-administration of 100 nM or higher levels of myo-inositol in the culture medium. Similarly, myo-inositol effectively restored the taurine transport activity suppressed by cyclosporin A (0.5 and 50 nM) in murine macrophages (p < 0.01). From these results, myo-inositol appears to be a common accelerator of taurine transport by murine macrophages in diverse conditions of down-regulated taurine transport.
Bibliographical noteFunding Information:
This work was supported by a grant No. R01-1999-000-00128-0 (2002) from the Basic Research Program of the Korea Science and Engineering Foundation. We greatly appreciate Dr. James E. Olson for his critical review of this manuscript.
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)