title: 1,25-hydroxyvitamin D relieves colitis in rats via down-regulation of toll-like receptor 9 expression.
abstract: OBJECTIVE
  To 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.
  
  
  METHODS
  Experimental 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.
  
  
  RESULTS
  Rats 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).
  
  
  CONCLUSIONS
  TLR9 expression correlates with the extent of inflammation in TNBS-induced colitis. 1,25(OH)D3 relieves this inflammation possibly by decreasing TLR9 expression.
authors.forename: Zhang-Han
authors.initials: ZH
authors.lastname: Dai
authors.forename: Bei
authors.initials: B
authors.lastname: Tan
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: Ou
authors.initials: O
authors.lastname: Wang
authors.forename: Jia-Ming
authors.initials: JM
authors.lastname: Qian
authors.affiliation: Lv Hong, No. 1 Shuai-fu-yuan, Dong-cheng Districts, Beijing, China, honglv2006@hotmail.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Lv
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D004359:Drug Therapy, Combination; D007249:Inflammation / Q000378:metabolism; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D051217:Toll-Like Receptor 9 / Q000096:biosynthesis*; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology; D014807:Vitamin D / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D014807:Vitamin D; D019804:Mesalamine; C097949:1,25-dihydroxyvitamin D; D014302:Trinitrobenzenesulfonic Acid