Low molecular weight heparin relieves experimental colitis in mice by downregulating IL-1β and inhibiting syndecan-1 shedding in the intestinal mucosa.

Cun-Long Chen,You-Lian Zhou,Shi-Yong Lin,Ai-Ming Li,Chu-Di Chen,Jing Li,Ye Chen,Si-De Liu,Xian-Fei Wang,Xia Wang

doi:10.1371/journal.pone.0066397

Cun-Long Chen, You-Lian Zhou + Show 8 more

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https://doi.org/10.1371/journal.pone.0066397

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Journal: PloS one	Publication Date: Jul 18, 2013
Citations: 26	License type: CC BY 4.0

Affiliation: Southern Medical University, Nanfang Hospital

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.

Highlights

Low molecular weight heparins (LMWHs) are mixtures of heparin molecules in the range of 3000 to 10,000 Daltons [1]
We investigated the effects of LMWH on dextran sulfate sodium (DSS)-induced colitis in mice, in which acute colitis progresses to chronic colitis
These results suggested that DSS could induce acute and chronic colitis accompanied with inflammatory responses in the mice

Summary

Introduction

Low molecular weight heparins (LMWHs) are mixtures of heparin molecules in the range of 3000 to 10,000 Daltons [1]. Syndecan-1 is a member of the syndecan family, which consists of the cell-surface heparan sulfate proteoglycans (HSPG) that regulate cell behavior by binding extracellular matrix molecules such as growth factors, cytokines, and even heparin-binding proteins on the bacterial surface [7]. Syndecan-1 plays an important role in promoting wound repair, maintaining cell morphogenesis, and mediating inflammatory responses [8]. Recent studies have shown that syndecan-1 is shed and released into the blood and that syndecan-1 shedding is an important mechanism by which neutrophilic inflammation is relieved by aiding the clearance of proinflammatory chemokines in a heparan sulfate-dependent manner [10,11,12]. Activated syndecan-1 shedding is observed in many pathological processes such as inflammatory response in the lung [13]

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