Effect of 1,25-dihydroxyvitamin D on all-trans retinoic acid metabolism and interleukin-4 signaling in porcine alternatively activated lung macrophages. (IRM7P.493)

Abstract

Abstract All-trans retinoic acid (ATRA), the most active vitamin A (VA) metabolite, and 1,25-dihydroxyvitamin D (VD3), the most active form of vitamin D (VD), and interleukin-4 (IL-4) each positively regulate the development of alternatively activated macrophages (AAM) however, their interactions are unknown. We have previously shown that VA, ATRA, and IL-4 have differing mechanisms for sustaining a Th2-type AAM response. Herein, we demonstrate that VD3 regulates the contribution of ATRA and IL-4 inducible signals to this system. While ATRA (10-7 M) increases mRNA expression of retinol producing dehydrogenase/reductase (SDR family) member, 4 fold, VD3 (10-7 M) decreases its expression 3-fold and additively increases expression of retinal producing, Aldehyde dehydrogenase 1 family, member A2, and dehydrogenase/reductase (SDR family) member 9 by 5 fold when present along with ATRA. Conversely, VD3 decreases IL-4 (10 ng/ml) -induced chemokine (C-C motif) ligand 17 by 4 fold, and C-type lectin CD209 antigen by 60 fold. These results suggest that VD3 increases expression of genes involved in ATRA anabolism while decreasing expression of IL-4 responsive genes. In conclusion, VD3 may regulate the development of AAM by increasing levels of ATRA and decreasing the effect of IL-4, thereby supporting an alternate signal for AAM development.