title: Low molecular weight heparin relieves experimental colitis in mice by downregulating IL-1β and inhibiting syndecan-1 shedding in the intestinal mucosa.
abstract: Low molecular weight heparin (LMWH) exhibits anti-inflammatory properties, but its effect on inflammation in colitis remains unclear. This study aimed to evaluate the therapeutic effects of LMWH on dextran sulfate sodium (DSS)-induced colitis in mice, in which acute colitis progresses to chronic colitis, and to explore the potential mechanism involved in this process. C57BL/6 mice were randomly divided into control, DSS, and DSS plus LMWH groups (n = 18). Disease activity was scored by a disease activity index (DAI). Histological changes were evaluated by hematoxylin and eosin (HE) staining. The mRNA levels of syndecan-1, interleukin (IL)-1β, and IL-10 were determined by quantitative reverse transcription polymerase chain reaction. Protein expression of syndecan-1 was detected by immunohistochemistry. The serum syndecan-1 level was examined by a dot immunobinding assay. LMWH ameliorated the disease activity of colitis induced by DSS administration in mice. Colon destruction with the appearance of crypt damage, goblet cell loss, and a larger ulcer was found on day 12 after DSS administration, which was greatly relieved by the treatment of LMWH. LMWH upregulated syndecan-1 expression in the intestinal mucosa and reduced the serum syndecan-1 level on days 12 and 20 after DSS administration (P<0.05 vs. DSS group). In addition, LMWH significantly decreased the expression of both IL-1β and IL-10 mRNA on days 12 and 20 (P<0.05 vs. DSS group). LMWH has therapeutic effects on colitis by downregulating inflammatory cytokines and inhibiting syndecan-1 shedding in the intestinal mucosa.
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Xian-fei
authors.initials: XF
authors.lastname: Wang
authors.forename: Ai-ming
authors.initials: AM
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Shi-yong
authors.initials: SY
authors.lastname: Lin
authors.forename: Chu-di
authors.initials: CD
authors.lastname: Chen
authors.forename: You-Lian
authors.initials: YL
authors.lastname: Zhou
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.forename: Cun-long
authors.initials: CL
authors.lastname: Chen
authors.forename: Si-de
authors.initials: SD
authors.lastname: Liu
authors.forename: Ye
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003092:Colitis / Q000188:drug therapy* / Q000209:etiology; D017931:DNA Primers / Q000235:genetics; D016264:Dextran Sulfate / Q000633:toxicity; D015536:Down-Regulation / Q000187:drug effects*; D006495:Heparin, Low-Molecular-Weight / Q000378:metabolism / Q000494:pharmacology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053668:Syndecan-1 / Q000097:blood*
chemical_list: D017931:DNA Primers; D006495:Heparin, Low-Molecular-Weight; D053583:Interleukin-1beta; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D016753:Interleukin-10; D016264:Dextran Sulfate