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Retinoids modulate many physiological processes such as the differentiation and growth of different cell types. including cells from the immune system. We have previously shown that retinoids modulate IgE production in vitro and in vivo. In the present study we investigated the effects of retinoids in non-sensitized and ovalbumin-sensitized mice that were fed for 11 weeks with three different vitamin A (VA) diets: a) VA-deficiency diet, b) base diet, and c) base diet supplemented with 0.5% all-trans-retinoic acid (ATRA). Phorbol-myristate-acetate (PMA)/ionomycin-stimulated SMC (splenic mononuclear cells) from mice fed with ATRA and the vitamin A-deficient diet group showed increased interleukin-4 (IL-4) responses in non-sensitized mice. After ovalbumin sensitization in the VA-deficient and the ATRA supplementation diet groups, no significant effects on IL-4 production were observed. By contrast, gamma interferon (IFN-gamma production from PMA/ionomycin-stimulated SMC was enhanced in the VA-deficient diet group in ovalbumin-sensitized mice, and also in non-sensitized mice compared to the base and the ATRA-supplemented diet group. The data indicate that VA and retinoid content in a diet influences the cytokine response in non-sensitized and also ovalbumin-sensitized mice. Therefore these molecules may serve as active modulators of cytokine production in vivo that are responsible for the induction and persistence of atopic diseases
14-Hydroxy-retro-retinol was previously described as an in vivo and in vitro metabolite of retinol. Furthermore, the retinoid 4-hydroxy-retinol was identified as an endogenous occurring retinoid in the amphibian organism and an in vitro metabolite of retinol. We describe in the present study that 14-hydroxy-retro-retinol and 4-hydroxy- retinol are present in normal neonatal rat serum as endogenous occurring retinoids in normal non-vitamin A supplemented mammals (rats). Both retinoids were detected in serum and liver of neonatal rats at days 3 and 11 after birth. The respective concentrations at day 11 after birth were 41.8 +/- 2.8 ng/ml (serum)/ 104 +/- 6 ng/g (liver) for 4-hydroxy- retinol and 23 +/- 4.6 ng/ml (serum)/ 285 +/- 5 ng/g (liver) for 14-hydroxy-retro-retinol. Both retinoids could not be detected in adult rat serum and liver. From our experiments important physiological functions of these retinoids during postnatal development could be postulated. (C) 2004 Elsevier Inc. All rights reserved