The ileal lipid binding protein (ilbp) is a cytoplasmic protein that binds bile acids with high affinity. However evidence demonstrating the role of this protein in bile acid transport and homeostasis is missing. We created a mouse strain lacking ilbp (Fabp6−/− mice) and assessed the impact of ilbp deficiency on bile acid homeostasis and transport in vivo. Elimination of ilbp increased fecal bile acid excretion (54.2%, P<0.05) in female but not male Fabp6−/− mice. The activity of cholesterol 7α-hydroxylase (cyp7a1), the rate-controlling enzyme of the classical bile acid biosynthetic pathway, was significantly increased in female (63.5%, P<0.05) but not in male Fabp6−/− mice. The amount of [3H]taurocholic acid (TCA) excreted by 24 h after oral administration was 102% (P<0.025) higher for female Fabp6−/− mice whereas it was 57.3% (P<0.01) lower for male Fabp6−/− mice, compared to wild-type mice. The retained fraction of the [3H]TCA localized in the small and large intestines was increased by 22% (P<0.02) and decreased by 62.7% (P<0.01), respectively, in male Fabp6−/− mice relative wild-type mice, whereas no changes were seen in female Fabp6−/− mice. Mucosal to serosal bile acid transport using everted distal gut sacs was decreased by 74% (P<0.03) in both sexes of Fabp6−/− mice as compared to wild-type mice. The results demonstrate that ilbp is involved in the apical to basolateral transport of bile acids in ileal enterocytes, and is vital for the maintenance of bile acid homeostasis in the enterohepatic circulation (EHC) in mice.
To determine the effect of different doses of Salmonella enteritidis on immunocompetent cells, the thymus, bursa of Fabricius, and peripheral blood were examined. One-day-old chickens were orally infected with 2 × 10 2 CFU/ml (low dose) and 2 × 10 8 CFU/ml (high dose) of S. enteritidis PT4. Subsets of T lymphocytes (CD3, CD4, and CD8), and BU1b cells using an indirect immunofluorescent method and flow cytometry were analysed on days 7, 10, 14, 21, and 27 postinoculation (dpi). The actual number of lymphocytes in the peripheral blood showed a significant increase in the low dose group (P < 0.05) on day 21 pi, and in the high dose group on day 27 pi (P < 0.001) compared to controls. The increase of CD3+, CD4+, and CD8+ T cells was observed in both infected groups compared to the controls from day 14 pi, significant on day 21 pi (P < 0.05) in the high dose group. The subpopulation of CD8+ was higher also on day 27 pi (P < 0.01) compared with the values of the control group. The subpopulation of BU1b+ B cells in both infected groups showed higher values, but without significant differences from controls. The thymus T lymphocytes showed a significant decline in CD3+ T cells on day 7 pi, whereas CD4+ T cells were significantly (P < 0.05) increased on day 7 pi in both infected groups. The bursal lymphocytes showed a decrease in BU1b+ B cells in both infected groups compared with the control group, significant in the high dose group on day 21 pi (P < 0.05). These results indicate that S. enteritidis infection induced the changes in immunocompetent cells, included cellular and humoral immune response. Salmonella infection accelerated the maturation and differentiation of thymus T cells in the first phase of infection, what was secondarily reflected by increased number of studied T lymphocyte subpopulations in the peripheral blood from day 14 to 27 after infection. Similarly, it appears that the activation of B cells in bursa of Fabricius caused the decrease number of bursal B lymphocytes and increased number of these cells in the peripheral blood from day 14 to 27 pi in both infected groups.
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