Abstract
PCR. IL-34 expression in the IBD mucosa was evaluated by immunohistochemical methods. In separate experiments human PBMC and human intestinal fibroblasts (HIF) were stimulated with IL-1β and TNF-α to study induction of IL-34 mRNA and protein. Protein levels were determined by immnoblotting. Finally SAMP-1/YitFc with CD-like ileitis were treated with Dexamethazone (Dex) at a dose of 5 mg/day body weight for 7 days and IL-34 and CSF-1 levels analyzed in intestinal tissue at the end of the experiment. Results: mRNA transcript levels of IL-34 were significantly increased in UC patients compared to CD patients and HC (p=0.05). In addition, IL-34 protein was detected predominantly in UC histological sections. Further characterization revealed that IL-34 mRNA is induced upon stimulation of both human PBMC as well as HIF with TNF-α and IL-1β while it is downregulated upon stimulation with TGF-β. Treatment of SAMP-1/YitFc mice with Dex was associated with downregulation of IL-34 compared to PBS-treated SAMP mice. Interestingly CSF-1 mRNA levels were elevated in Dex-treatedmice, indicating a reciprocal secretion pattern and possibly function between IL-34 and CSF-1. Conclusion: Taken together these data demonstrate that IL-34 is specifically increased in UC patients and is modulated by proand antiinflammatory factors in both human tissue and murine model of chronic intestinal inflammation.
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