Dexamethasone recovers phorbol-ester induced reduction of taurine transportation in mouse macrophage cell line, RAW 264.7.

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The human taurine transporter gene has 12 transmembrane domains and its molecular weight is 69.6 kDa. The long cytoplasmic carboxy and amino termini might function as regulatory attachment sites for other proteins. Six potential protein kinase C phosphorylation sites have been reported in human taurine transporter. In this report, we studied the effects of phorbol 12-myristate 13-acetate (PMA) and glucocorticoid hormone on the taurine transportation in RAW 264.7, a mouse macrophage cell line. When the cells were incubated with [3H]taurine in the presence or absence of Na+ ion for 40 min at 37°C, [3H]taurine uptake rate was 780-times higher in the Na+-containing buffer than in the Na+-deficient buffer, indicating that this cell line expresses taurine transporter protein on the cell surface. THP1, human promonocyte cell line, also showed a similar property. The [3H]taurine uptake rate was not influenced by the inflammatory-inducing cytokines such as interleukin-1, gamma-interferon or interleukin-1 + gamma-interferon, but was decreased by PMA in the RAW 264.7 cell line. This suggests that activation of protein kinase C inhibits taurine transporter activity directly or indirectly. The inhibition of [3H]taurine uptake by PMA was time-dependent. Maximal inhibition occurred with 1 h stimulation with PMA. Increasing the treatment time beyond 1 h reduced the inhibition of [3H]taurine uptake, due to the depletion or inactivation of protein kinase C. The cell line also showed concentration-dependent [3H]taurine uptake by PMA stimulation. Phorbol ester (1 μM) caused 23% inhibition. The inhibition was significant even at a concentration as low as 10 nM PMA. The reduced [3H]taurine uptake could be reversed by treatment with glucocorticosteroid hormone. Dexamethasone recovered the reduced taurine uptake induced by phorbol ester, the maximum effect being seen at 1 h. This may suggest that macrophage cells require higher taurine concentration in a stressed state, for the secretion of glucocorticoid hormone is increased by hypothalamo-pituitary-adrenocortical axis activation in the blood stream.