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Clotrimazole inhibits inflammation and pathogenic angiogenesis via modulation of IL‐8 in TNF‐α‐induced intestinal inflammation
Author(s) -
Thapa Dinesh,
Kwon Jun Bum,
Park Byung Chul,
Kim JungAe
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1138.2
Subject(s) - angiogenesis , inflammation , tumor necrosis factor alpha , in vivo , immunology , pathogenesis , downregulation and upregulation , cytokine , cancer research , medicine , chemistry , biology , biochemistry , microbiology and biotechnology , gene
In the inflammatory bowel diseases (IBD), tissue level of interleukin (IL)‐8 has been reported to be upregulated. Such increased IL‐8 activates and recruits leukocytes to the inflamed site. Recent evidences have shown that IL‐8 also induces angiogenesis at the inflammation site, which further aggravates the condition of IBD. Since clotrimazole (CLT) has been reported to inhibit angiogenesis, in the present study, we investigated whether CLT inhibits intestinal inflammation via its inhibitory action on IL‐8. In TNF‐α‐stimulated HT29 colon epithelial cells, a well recognized in vitro model for colon inflammation, the treatment with CLT significantly suppressed TNF‐α‐induced increase in IL‐8 level at both mRNA and secreted protein levels. In addition, CLT inhibited both TNF‐α‐ and IL‐8‐induced monocyte adhesion to the cells and MCP‐1 expression in a concentration‐dependent manner. In an in vitro angiogenesis assay, CLT suppressed IL‐8‐induced proliferation, tube formation, and invasion of endothelial cells. In addition, CLT inhibited the IL‐8‐induced angiogenesis in vivo using a chick chorioalantoic membrane assay. Collectively, these results suggest that CLT may prevent the progression of intestinal inflammation by not only down‐regulating IL‐8 expression but also inhibiting the action of IL‐8 in both colon epithelial and endothelial cells during pathogenesis of IBD.