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The selective nonpeptide CXCR2 antagonist SB225002 ameliorates acute experimental colitis in mice.
J Leukoc Biol. 2008 Oct; 84(4):1213-21.JL

Abstract

Although neutrophils are strongly implicated in eliminating pathogens, excessive recruitment may cause tissue damage. Therefore, reducing cell influx during an inflammatory process may be a potential target for treating inflammatory bowel diseases (IBD). As CXCR2 is involved in neutrophil migration, this study aimed to evaluate whether the systemic therapeutic treatment with selective CXCR2 antagonist SB225002 ameliorates experimental colitis, which was induced in mice by 2,4,6-trinitrobenzene sulfonic acid (TNBS). After colitis establishment (24 h), mice were treated with SB225002. At later time-points, up to 72 h, mice were monitored for body weight loss and overall mortality. At the time of sacrifice, colonic tissues were scored for macro- and microscopic damage, and cytokine levels, myeloperoxidase (MPO) activity, and protein expression were analyzed. TNBS administration induced macro- and microscopic damage in colon tissue, leading in most cases to animal death. Curative treatment with SB225002 significantly reduced all of the parameters analyzed, leading to an improvement of inflammatory signs. SB225002 reduced neutrophil influx, MPO activity, IL-1beta, MIP-2, and keratinocyte-derived chemokine (KC) levels and the expression of vascular endothelial growth factor, inducible NO synthase, and cyclooxygenase-2 proteins into the colon tissue. Levels of IL-4 and IL-10 were increased significantly in the colons of animals treated with SB225002. Additionally, curative treatment with mouse anti-KC significantly reduced MPO activity and colonic damage. These results taken together demonstrate that a selective blockade of CXCR2 consistently reduced TNBS-induced colitis, suggesting that the use of SB225002 is a potential therapeutic approach for the treatment of IBD and other related inflammatory disorders.

Authors+Show Affiliations

Universidade Federal de Santa Catarina, Campus Universitário, CEP 88049-900, Florianópolis, SC, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18653784

Citation

Bento, Allisson Freire, et al. "The Selective Nonpeptide CXCR2 Antagonist SB225002 Ameliorates Acute Experimental Colitis in Mice." Journal of Leukocyte Biology, vol. 84, no. 4, 2008, pp. 1213-21.
Bento AF, Leite DF, Claudino RF, et al. The selective nonpeptide CXCR2 antagonist SB225002 ameliorates acute experimental colitis in mice. J Leukoc Biol. 2008;84(4):1213-21.
Bento, A. F., Leite, D. F., Claudino, R. F., Hara, D. B., Leal, P. C., & Calixto, J. B. (2008). The selective nonpeptide CXCR2 antagonist SB225002 ameliorates acute experimental colitis in mice. Journal of Leukocyte Biology, 84(4), 1213-21. https://doi.org/10.1189/jlb.0408231
Bento AF, et al. The Selective Nonpeptide CXCR2 Antagonist SB225002 Ameliorates Acute Experimental Colitis in Mice. J Leukoc Biol. 2008;84(4):1213-21. PubMed PMID: 18653784.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The selective nonpeptide CXCR2 antagonist SB225002 ameliorates acute experimental colitis in mice. AU - Bento,Allisson Freire, AU - Leite,Daniela Ferraz Pereira, AU - Claudino,Rafaela Franco, AU - Hara,Daniela Balz, AU - Leal,Paulo César, AU - Calixto,João B, Y1 - 2008/07/24/ PY - 2008/7/26/pubmed PY - 2008/11/5/medline PY - 2008/7/26/entrez SP - 1213 EP - 21 JF - Journal of leukocyte biology JO - J. Leukoc. Biol. VL - 84 IS - 4 N2 - Although neutrophils are strongly implicated in eliminating pathogens, excessive recruitment may cause tissue damage. Therefore, reducing cell influx during an inflammatory process may be a potential target for treating inflammatory bowel diseases (IBD). As CXCR2 is involved in neutrophil migration, this study aimed to evaluate whether the systemic therapeutic treatment with selective CXCR2 antagonist SB225002 ameliorates experimental colitis, which was induced in mice by 2,4,6-trinitrobenzene sulfonic acid (TNBS). After colitis establishment (24 h), mice were treated with SB225002. At later time-points, up to 72 h, mice were monitored for body weight loss and overall mortality. At the time of sacrifice, colonic tissues were scored for macro- and microscopic damage, and cytokine levels, myeloperoxidase (MPO) activity, and protein expression were analyzed. TNBS administration induced macro- and microscopic damage in colon tissue, leading in most cases to animal death. Curative treatment with SB225002 significantly reduced all of the parameters analyzed, leading to an improvement of inflammatory signs. SB225002 reduced neutrophil influx, MPO activity, IL-1beta, MIP-2, and keratinocyte-derived chemokine (KC) levels and the expression of vascular endothelial growth factor, inducible NO synthase, and cyclooxygenase-2 proteins into the colon tissue. Levels of IL-4 and IL-10 were increased significantly in the colons of animals treated with SB225002. Additionally, curative treatment with mouse anti-KC significantly reduced MPO activity and colonic damage. These results taken together demonstrate that a selective blockade of CXCR2 consistently reduced TNBS-induced colitis, suggesting that the use of SB225002 is a potential therapeutic approach for the treatment of IBD and other related inflammatory disorders. SN - 0741-5400 UR - https://www.unboundmedicine.com/medline/citation/18653784/The_selective_nonpeptide_CXCR2_antagonist_SB225002_ameliorates_acute_experimental_colitis_in_mice_ L2 - https://doi.org/10.1189/jlb.0408231 DB - PRIME DP - Unbound Medicine ER -