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Local production of chemokines and prostaglandin E2 in the acute, chronic and recovery phase of murine experimental colitis

Department of Integrative Pharmacology, AstraZeneca R&D Mölndal, GI Biology, SE-431 83, Sweden.
Cytokine (Impact Factor: 2.66). 10/2006; 35(5-6):275-83. DOI: 10.1016/j.cyto.2006.09.007
Source: PubMed

ABSTRACT

Increased levels of chemokines and prostaglandins have been reported in patients with inflammatory bowel disease, although their changes during disease development are less understood. The aim of this study was to investigate the local production of nine selected chemokines and prostaglandin E(2) (PGE(2)) to elucidate their role in colitis progression in BALB/c and C57BL/6 mice exposed to dextran sulphate sodium. The acute inflammation in both strains was accompanied by a significant up-regulation of CXCL1, CXCL2/3, CXCL10, CCL2, CCL4 and CCL22 and a downregulation of PGE(2). In the recovery phase in BALB/c, one-week post-DSS, PGE(2) levels were significantly increased with a concomitant downregulation of CXCL1, CXCL2/3, CXCL10, CCL2, and CCL4. In contrast, in C57BL/6 mice CXCL1, CXCL2/3, CXCL10, CCL2, CCL3 and CCL4 production remained high during the chronic phase, without any up-regulation of PGE(2). In addition, CCL5 was significantly increased at d26 and 33 compared to d5. Interestingly, the number of macrophages was significantly increased during the acute phase, whereas T cells were significantly increased in both the acute and chronic phase in C57BL/6 mice. Thus, our results show that chemokines are produced in a dynamic manner during colitis progression.

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    • "Inflammation in experimentally induced colitis is characterized by increased PGs such as PGE 2 and PGD 2 . PGD 2 (Ajuebor et al, 2000; Melgar et al, 2006) is further converted by dehydratation to 15-deoxy- 12,14 -PGJ 2 (15d-PGJ 2 ) (Monneret et al, 2002), a stable PG and putative endogenous PPAR ligand with cytoprotective and anti-inflammatory properties, and hence a new potential therapeutic target in inflammatory bowel diseases (Dubuquoy et al, 2006). 7-Hydroxy-DHEA, the innate metabolite of dehydroepiandrosterone (DHEA), is normally produced in the colon and many other tissues (Doostzadeh & Morfin, 1996; Morfin & Courchay, 1994) but overproduced by IL-1β during the inflammatory process as shown in mice and humans (Dulos et al, 2004; Dulos et al, 2005). "

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    • "Clinical symptoms in the models are body weight loss, diarrhoea, and hunched posture. The histopathological characteristics of the DSS model include distorted epithelial and crypt architecture, infiltration of neutrophils and macrophages early in disease progression accompanied by T and B cell infiltration later in the inflammation [2] [3]. Infiltration of inflammatory cells induces production of pro-inflammatory mediators, e.g. "
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    • "e early phase of DSS-induced colitis (Murano et al., 2000;Melgar et al., 2006). On the other hand, the sustained increase of CXCR4 expression on peripheral T cells at the late phase of DSS-induced colitis, as observed in the present study, suggests that T cells are involved in sustained colonic inflammation after DSS administration in C57BL/6 mice.Melgar et al. (2006)reported that only 5-day administration of DSS induces chronic inflammation of the colon in C57BL/6 mice. Taken together, the increased expression of CXCR4 on T cells might mainly contribute to the development of chronic colitis induced by DSS administration. An important finding of our study is that blocking the CXCL12/CXCR4 chemotaxis "
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