Dexamethasone and lipopolysaccharide regulation of taurine transport in Caco-2 cells.
Intracellular enterocytic levels of the immunomodulator taurine decrease significantly in response to trauma and surgical insult. The effect of physiological stress on enterocyte taurine uptake is unknown. The aim of this study was to compare taurine transport under basal and stressed conditions using the human intestinal Caco-2 cell line in vitro. Caco-2 cells were incubated with 10 nM [1,2-3H]taurine at 37 degrees C and 5% CO2 and taurine uptake was examined over the range of 0.1-10 microM to determine kinetic parameters of the transporter. The culture medium was then supplemented with dexamethasone and/or lipopolysaccharide (LPS) and taurine uptake was calculated as picomoles per milligram protein per hour. Statistics were by unpaired Student's t test. Taurine uptake was hyperbolically related to taurine concentration and obeyed Michaelis-Menten kinetics with a K(m) of 5.27 +/- 0.95 microM and Vmax of 1125.43 +/- 130.9 pmole/mg protein/ hour. Dexamethasone (1-1000 microM) significantly reduced taurine uptake by up to 66.15%. LPS (1 microgram/ml) impaired transport of taurine by 15.7%, and in combination with dexamethasone (100 microM) by 42.4%. All results are mean of at least three experiments and P < 0.05. We have established that taurine uptake by enterocytes is downregulated by dexamethasone. This may relate to the decreased intestinal levels of taurine observed in trauma and surgery patients. Further study may elucidate mechanisms whereby homeostasis of enterocyte taurine might be maintained during sepsis.
O'Flaherty
L
L
Royal College of Surgeons in Ireland, Department of Surgery, Beaumont Hospital, Dublin, Ireland.
Stapleton
P P
PP
Redmond
H P
HP
Bouchier-Hayes
D
D
D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008871:Microvilli / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism*; D013654:Taurine / Q000378:metabolism*
D005938:Glucocorticoids; D008070:Lipopolysaccharides; D013654:Taurine; D003907:Dexamethasone