Inflammatory bowel disease is characterized with uncontrolled immune response in inflamed mucosa, with dominance of Th1 cells. Recently,
all-trans retinoic acid has been shown that can lead T-cell response by suppressing Th17 development via
retinoic acid receptor (RAR), but it is still unknown whether
all-trans retinoic acid can modulate Th1 response of
inflammatory bowel disease. In the experiment, we investigated the effect of
all-trans retinoic acid on trinitrobenzene
sulfonic acid (TNBS)-induced murine
colitis, and the possible mechanism. Mice were intraperitoneally treated daily with
all-trans retinoic acid (the agonist of RAR-alpha) or
LE135 (the antagonist of RAR-alpha) or medium, and sacrificed 6 days later. Colon was collected for histological analysis and
myeloperoxidase (MPO) activity measurement. Lamina propria mononuclear cells (LPMCs) were isolated, cultured, and assayed for the expressions of T-bet and GATA-3 by the use of Western blot and for
cytokine levels by the use of ELISA.
All-trans retinoic acid treatment inhibited inflammatory responses as shown by lower histological inflammatory scores and MPO activity, compared with
LE135 and medium groups. Furthermore, in LPMCs culture supernatants, the levels of Th1
cytokines (INF-gamma, IL-12, and TNF-alpha) were decreased while those of Th2
cytokines (IL-4 and IL-10) were increased significantly in
all-trans retinoic acid-treated mice. In addition, T-bet expression in LPMCs was inhibited and GATA-3 expression was up-regulated in all-trans retinoic acidtreated mice. On the contrary,
LE135 showed the reverse effects in colon
inflammation and
cytokine profile. By shifting Th1 to Th2 profile in inflamed mucosa,
all-trans retinoic acid down-regulates inflammatory response and ameliorates acute TNBS-induced
colitis, which suggests the
ligand of RAR-alpha-based
pharmaceutical strategies for managing
inflammatory bowel disease.