First Author | Skyberg JA | Year | 2011 |
Journal | J Leukoc Biol | Volume | 90 |
Issue | 6 | Pages | 1043-54 |
PubMed ID | 21693591 | Mgi Jnum | J:179191 |
Mgi Id | MGI:5301248 | Doi | 10.1189/jlb.0311168 |
Citation | Skyberg JA, et al. (2011) Apple polyphenols require T cells to ameliorate dextran sulfate sodium-induced colitis and dampen proinflammatory cytokine expression. J Leukoc Biol 90(6):1043-54 |
abstractText | Human IBD, including UC and Crohn's disease, is characterized by a chronic, relapsing, and remitting condition that exhibits various features of immunological inflammation and affects at least one/1000 people in Western countries. Polyphenol extracts from a variety of plants have been shown to have immunomodulatory and anti-inflammatory effects. In this study, treatment with APP was investigated to ameliorate chemically induced colitis. Oral but not peritoneal administration of APP during colitis induction significantly protected C57BL/6 mice against disease, as evidenced by the lack of weight loss, colonic inflammation, and shortening of the colon. APP administration dampened the mRNA expression of IL-1beta, TNF-alpha, IL-6, IL-17, IL-22, CXCL9, CXCL10, CXCL11, and IFN-gamma in the colons of mice with colitis. APP-mediated protection requires T cells, as protection was abated in Rag-1(-/-) or TCRalpha(-/-) mice but not in IL-10(-/-), IRF-1(-/-), muMT, or TCRdelta(-/-) mice. Administration of APP during colitis to TCRalpha(-/-) mice actually enhanced proinflammatory cytokine expression, further demonstrating a requirement for TCRalphabeta cells in APP-mediated protection. APP treatment also inhibited CXCR3 expression by TCRalphabeta cells, but not B or NK cells, in the colons of mice with colitis; however, depletion of CD4(+) or CD8(+) T cells alone did not abolish APP-mediated protection. Collectively, these results show that oral administration of APP protects against experimental colitis and diminishes proinflammatory cytokine expression via T cells. |