The COX-2 inhibitor, rofecoxib, ameliorates dextran sulphate sodium induced colitis in mice

Martín, Antonio; Villegas, Isabel; Lastra, Catalina Alarcón de la

doi:10.1007/s00011-004-1337-2

Cited by 49 publications

(39 citation statements)

References 42 publications

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“…Furthermore, we demonstrate that PGE2 production induced by SCFAs was inhibited by a COX-1 inhibitor, but not a COX-2 inhibitor. This is consistent with the notion that in DSS-induced colitis, the significant reduction in PGE2 resulted from decreased expression of COX-1, but not COX-2 [33] . In human monocytes, SCFAs specifically inhibited constitutive MCP-1 production and LPS-induced IL-10 production out of the total 16 cytokines and chemokines examined.…”

Section: Discussionsupporting

confidence: 91%

Short-chain fatty acids act as antiinﬂammatory mediatorsby regulating prostaglandin E2 and cytokines

Cox¹,

Jackson²,

Stanton³

et al. 2009

WJG

330

244

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AIM:To investigate the effect of short-chain fatty acids (SCFAs) on production of prostaglandin E2 (PGE2), cytokines and chemokines in human monocytes. METHODS:Human neutrophils and monocytes were isolated from human whole blood by using 1-Step Polymorph and RosetteSep Human Monocyte Enrichment Cocktail, respectively. Human GPR41 and GPR43 mRNA expression was examined by quantitative realtime polymerase chain reaction. The calcium flux assay was used to examine the biological activities of SCFAs in human neutrophils and monocytes. The effect of SCFAs on human monocytes and peripheral blood mononuclear cells (PBMC) was studied by measuring PGE2, cytokines and chemokines in the supernatant.The effect of SCFAs in vivo was examined by intraplantar injection into rat paws. RESULTS:Human GPR43 is highly expressed in human neutrophils and monocytes. SCFAs induce robust calcium flux in human neutrophils, but not in human monocytes. In this study, we show that SCFAs can induce human monocyte release of PGE2 and that this effect can be enhanced in the presence of lipopolysaccharide (LPS). In addition, we demonstrate that PGE2 production induced by SCFA was inhibited by pertussis toxin, suggesting the involvement of a receptor-mediated mechanism. Furthermore, SCFAs can specifically inhibit constitutive monocyte chemotactic protein-1 (MCP-1) production and LPS-induced interleukin-10 (IL-10) production in human monocytes without affecting the secretion of other cytokines and chemokines examined. Similar activities were observed in human PBMC for the release of PGE2, MCP-1 and IL-10 after SCFA treatment. In addition, SCFAs inhibit LPS-induced production of tumor necrosis factor-α and interferon-γ in human PBMC. Finally, we show that SCFAs and LPS can induce PGE2 production in vivo by intraplantar injection into rat paws (P < 0.01). CONCLUSION:SCFAs can have distinct antiinflammatory activities due to their regulation of PGE2, cytokine and chemokine release from human immune cells.

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Section: Discussionsupporting

confidence: 91%

Short-chain fatty acids act as antiinﬂammatory mediatorsby regulating prostaglandin E2 and cytokines

Cox¹,

Jackson²,

Stanton³

et al. 2009

WJG

330

244

View full text Add to dashboard Cite

show abstract

“…To our knowledge, no previous studies have addressed this question, but several studies have used Cox-2 inhibitors in clinical trials (22) or in different animal models of colitis. The results from these studies range from Cox-2 inhibitors protecting from intestinal damage and colitis (10,24) to worsening the pathology and delaying the healing process (26,35). A similar range of conclusions was reported from studies addressing the role of Cox-2 in liver and lung fibrosis.…”

Section: Discussionmentioning

confidence: 69%

MyD88 signaling promotes both mucosal homeostatic and fibrotic responses during Salmonella-induced colitis

Månsson

Montero

Zarepour

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…This is in agreement with previous reports showing no significant amelioration in disease pathology when prednisone was added after TNBS addition (Woodruff et al, 2003), probably because of the delayed time it takes for steroids to become effective and their tendency to inhibit natural healing processes associated with disease pathology. Measurement of MPO activity has been widely used as a reliable index of neutrophil infiltration in colon (Martín et al, 2005). We found a high increase in MPO activity in the colon of TNBS-injected rats (Fig.…”

Section: Anti-inflammatory Action Of Edelfosine Without Toxicity 443mentioning

confidence: 61%

Novel Anti-Inflammatory Action of Edelfosine Lacking Toxicity with Protective Effect in Experimental Colitis

Mollinedo

Gajate²,

Morales³

et al. 2009

J Pharmacol Exp Ther

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Edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine; ) is an antitumor alkyl-lysophospholipid analog that binds lipid rafts, altering their protein composition (J Exp Med 200:353-365). Because L-selectin locates in lipid rafts and plays a crucial role in the recruitment of leukocytes into inflamed tissues, we hypothesized that edelfosine might affect inflammation by modulating L-selectin and inflammatory cell migration. Here, we have found that edelfosine inhibited neutrophil-endothelium interaction through L-selectin shedding. Oral treatment of edelfosine diminished inflammation in two murine animal models. Edelfosine showed a higher antiinflammatory effect than the nonsteroidal anti-inflammatory drug (NSAID) indomethacin in the bentonite mouse-paw edema model. Using a rat model of experimental colitis, edelfosine oral administration ameliorated the clinical and histopathologic severity of the inflammatory colitis with a dramatic decrease in mucosal damage and neutrophil infiltration. Colon sections from edelfosine-treated rats showed a remarkable reduction in ulcer formation, edema, and inflammatory cell infiltration. Edelfosine enhanced lipopolysaccharide-induced expression of anti-inflammatory interleukin-10 in mouse macrophages. Edelfosine oral treatment in rats, at doses 8-fold higher than those displaying anti-inflammatory action, lacked toxicity. Edelfosine treatment showed no any significant cardiotoxicity, hepatotoxicity or renal toxicity. Unlike NSAIDs, edelfosine did not inhibit prostaglandin E 2 synthesis in gastrointestinal mucosal biopsies, and no histologic alteration in gastrointestinal tract was detected after drug treatment. Thus, edelfosine shows a potent in vitro and in vivo anti-inflammatory activity while sparing gastric mucosa. Our data identify edelfosine as a novel anti-inflammatory drug by abating neutrophil infiltration through L-selectin shedding and may provide a new therapeutic approach for inflammatory bowel disease free from toxicity.

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The COX-2 inhibitor, rofecoxib, ameliorates dextran sulphate sodium induced colitis in mice

Abstract: Rofecoxib is protective in acute DSS-induced colitis, probably by reducing neutrophil infiltration, inhibiting up-regulation of IL-1beta and returning to normal COX-1 expression in the inflamed colonic mucosa.

Cited by 49 publications

References 42 publications

Short-chain fatty acids act as antiinﬂammatory mediatorsby regulating prostaglandin E2 and cytokines

Short-chain fatty acids act as antiinﬂammatory mediatorsby regulating prostaglandin E2 and cytokines

MyD88 signaling promotes both mucosal homeostatic and fibrotic responses during Salmonella-induced colitis

Novel Anti-Inflammatory Action of Edelfosine Lacking Toxicity with Protective Effect in Experimental Colitis

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