Publications (2)17.07 Total impact
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Article: IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6.
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ABSTRACT: Uncontrolled mucosal immunity in the gastrointestinal tract of humans results in chronic inflammatory bowel disease (IBD), such as Crohn disease and ulcerative colitis. In early clinical trials as well as in animal models, IL-12 has been implicated as a major mediator of these diseases based on the ability of anti-p40 mAb treatment to reverse intestinal inflammation. The cytokine IL-23 shares the same p40 subunit with IL-12, and the anti-p40 mAbs used in human and mouse IBD studies neutralized the activities of both IL-12 and IL-23. IL-10-deficient mice spontaneously develop enterocolitis. To determine how IL-23 contributes to intestinal inflammation, we studied the disease susceptibility in the absence of either IL-23 or IL-12 in this model, as well as the ability of recombinant IL-23 to exacerbate IBD induced by T cell transfer. Our study shows that in these models, IL-23 is essential for manifestation of chronic intestinal inflammation, whereas IL-12 is not. A critical target of IL-23 is a unique subset of tissue-homing memory T cells, which are specifically activated by IL-23 to produce the proinflammatory mediators IL-17 and IL-6. This pathway may be responsible for chronic intestinal inflammation as well as other chronic autoimmune inflammatory diseases.Journal of Clinical Investigation 06/2006; 116(5):1310-6. · 15.39 Impact Factor -
Article: Accelerated alveolar bone loss in mice lacking interleukin-10: late onset.
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ABSTRACT: Interleukin-10 (IL-10) is an anti-inflammatory cytokine regulating immune responses. We have previously reported that IL-10(-/-) mice experience accelerated alveolar bone loss. The purpose of the present study was to examine the timing of the manifestation of accelerated alveolar bone loss in IL-10(-/-) mice. Twenty-four IL-10(-/-) and 21 IL-10(+/+) age-matched male 129/SvEv mice were used. Sacrifice times occurred at 1, 3 and 9.5 months of age. Alveolar bone loss was determined morphometrically on defleshed jaws. Enzyme-linked immunosorbent assay (ELISA) was used for determination of serum concentration of type I collagen C-telopeptide, a systemic marker of bone resorption. Alveolar bone loss for the entire IL-10(-/-) group was significantly different than for the IL-10(+/+) group (p = 0.025). There was no significant difference in alveolar bone loss between IL-10(-/-) and IL-10(+/+) mice at 1 and 3 months of age. At 9.5 months of age, IL-10(-/-) mice exhibited 39% greater alveolar bone loss than IL-10(+/+) mice (p = 0.018). For IL-10(-/-) mice, alveolar bone loss significantly increased with age. Serum C-telopeptide levels significantly decreased with age in both groups. IL-10(-/-) mice had consistently higher C-telopeptide levels than IL-10(+/+) mice and the difference between the two groups reached statistical significance (p = 0.011) for the 9.5-month-old mice. These results suggest that the accelerated alveolar bone loss observed in IL-10(-/-) mice is a late-onset condition and that lack of IL-10 may have an effect on bone homeostasis.Journal of Periodontal Research 07/2004; 39(3):194-8. · 1.69 Impact Factor
