Local production of chemokines and prostaglandin E2 in the acute, chronic and recovery phase of murine experimental colitis.
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.
Melgar
Silvia
S
Department of Integrative Pharmacology, AstraZeneca R&D Mölndal, GI Biology, SE-431 83, Sweden. silvia.melgar@astrazeneca.com
Drmotova
Marketa
M
Rehnström
Erika
E
Jansson
Liselotte
L
Michaëlsson
Erik
E
D000208:Acute Disease; D000818:Animals; D000925:Anticoagulants / Q000633:toxicity; D018925:Chemokines / Q000096:biosynthesis* / Q000276:immunology; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000534:rehabilitation; D016264:Dextran Sulfate / Q000633:toxicity; D015232:Dinoprostone / Q000096:biosynthesis* / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000534:rehabilitation; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D000925:Anticoagulants; D018925:Chemokines; D016264:Dextran Sulfate; D015232:Dinoprostone