• Croatian medical journal · Dec 2015

    1,25-hydroxyvitamin D relieves colitis in rats via down-regulation of toll-like receptor 9 expression.

    • Zhang-Han Dai, Bei Tan, Hong Yang, Ou Wang, Jia-Ming Qian, and Hong Lv.
    • Lv Hong, No. 1 Shuai-fu-yuan, Dong-cheng Districts, Beijing, China, honglv2006@hotmail.com.
    • Croat. Med. J. 2015 Dec 1; 56 (6): 515524515-24.

    AimTo investigate the therapeutic and immunoregulatory effects of 1,25-dihydroxyvitamin D (1,25(OH)D3) on 2,4,6-trinitrobenzenesulfonic acid (TNBS) -induced colitis in rats.MethodsExperimental colitis induced by enema administration of TNBS plus ethanol was treated with 5-aminosalicylic acid (5-ASA) and/or 1,25(OH)D3. Disease activity was measured using the disease activation index (DAI), colon macroscopic damage index (CMDI), histological colonic damage score, and myeloperoxidase (MPO) activity. The expression of toll-like receptor 9 (TLR9) in the colon was determined by reverse transcription-polymerase chain reaction and immunohistochemistry.ResultsRats with TNBS-induced colitis had significantly elevated DAI, CMDI, histological colonic damage score, and MPO activity (all P<0.001) compared to rats without colitis. Treatment with 5-ASA or 1,25(OH)D3 ameliorated colitis by lowering CMDI (P=0.049, P=0.040, respectively), histological colonic damage score (P=0.010, P=0.005, respectively), and MPO activity (P=0.0003, P=0.0013, respectively) compared with the TNBS group. Combined treatment with 5-ASA and 1,25(OH)D3 significantly decreased MPO activity (P=0.003). 1,25(OH)D3 attenuated colitis without causing hypercalcemia or renal insufficiency. TNBS significantly increased the number of TLR9 positive cells compared to control (P<0.010), while 5-ASA, 1,25(OH)D3, and combined treatment with 5-ASA and 1,25(OH)D3 significantly decreased it compared to TNBS group (all P<0.010). In TNBS group a moderate correlation was observed between MPO activity and the number of TLR9-positive cells (r=0.654, P<0.001).ConclusionTLR9 expression correlates with the extent of inflammation in TNBS-induced colitis. 1,25(OH)D3 relieves this inflammation possibly by decreasing TLR9 expression.

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