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Curcumin inhibited the development of TAA-induced liver cirrhosis mainly due to its anti-inflammatory activities and not by a direct anti-fibrotic effect. As curcumin ingestion is safe in humans, it may be reasonable to assess in clinical studies the beneficial effect of curcumin in slowing the development of liver cirrhosis.

T-and natural killer (NK)-cell immunosuppression associated with -chain downregulation has been described in cancer, autoimmune, and infectious diseases. However, the precise stimuli leading to this bystander phenomenon in such different pathogen-dependent and sterile pathologies remained unresolved. Here, we demonstrate that Toll-like receptors (TLRs) play a major role in the induction of innate and adaptive immune system suppression; repetitive administration of single TLR 2, 3, 4, or 9 agonists, which do not exhibit any virulent or immune invasive properties, was sufficient to induce a bystander NK-and T-cell immunosuppression associated with -chain downregulation mediated by myeloid suppressor cells, as observed in the course of active pathologies. We identified a 35-amino acid (aa) region within the -chain as being responsible for its degradation under TLR-mediated chronic inflammation. Furthermore, we provide evidence that -chain levels could serve as a biomarker for chronic inflammationdependent immunosuppression. Thus, although acute TLR-mediated activation could be beneficial in clearing pathogens or may serve as an immune adjuvant, such activation could be detrimental under sustained conditions. (Blood. 2008;

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ObjectiveTo evaluate the effects of halofuginone, a specific inhibitor of collagen type synthesis, on the postoperative formation of abdominal adhesions in rats. Summary Background Data ResultsThe adhesions formed between the intestinal walls were composed of collagen and were populated with cells expressing the collagen al (1) gene. Regardless of the administration procedure, halofuginone significantly reduced the number and severity of the adhesions. Halofuginone prevented the increase in collagen al (1) gene expression observed in the operated rats, thus reducing collagen content to the control level. In fibroblasts derived from abdominal adhesions, halofuginone induced dose-dependent inhibition of collagen al (1) gene expression and collagen synthesis. Collagen type Ill levels were not altered by adhesion induction or by halofuginone treatment. ConclusionsUpregulation of collagen synthesis appears to have a critical role in the pathophysiology of postoperative adhesions. Halofuginone, an inhibitor of collagen type synthesis, could be used as an important tool in understanding the role of collagen in adhesion formation, and it may become a novel and promising antifibrotic agent for preventing postoperative adhesion formation.