Indoleamine 2,3-dioxygenase (IDO) catalyzes the degradation of tryptophan, which plays a critical role in immune suppression through regulating the production of a series of metabolites that are generally referred to as kynurenines. It has become increasingly clear that epithelial cells (ECs) play an active role in maintaining lung homeostasis by modulating the function of immune cells via producing cytokines, chemokines, and anti-microbial mediators. In this study we assessed the regulation of IDO activity and expression in human primary ECs and EC lines under steady state conditions and in response to bacterial and allergenic stimuli. We also investigated the potential immune modulatory functions of IDO expression in human airway ECs. Our data clearly show that airway ECs produce IDO, which is down-regulated in response to allergens and TLR ligands while up-regulated in response to IFN-γ. Using gene silencing, we further demonstrate that IDO plays a key role in the EC-mediated suppression of antigen-specific and polyclonal proliferation of T cells. Interestingly, our data also show that ECs lose their inhibitory effect on T cell activation in response to different TLR agonists mimicking bacterial or viral infections. In conclusion, our work provides an understanding of how IDO is regulated in ECs as well as demonstrates that “resting” ECs can suppress T cell activation in an IDO dependent manner. These data provide new insight into how ECs, through the production of IDO, can influence downstream innate and adaptive responses as part of their function in maintaining immune homeostasis in the airways.

Herbal medicine has been in use for centuries for a wide variety of ailments; however, the efficacy of its therapeutic agents in modern medicine is currently being studied. Curcuminoids are an example of natural agents, widely used due to their potential contribution in the prevention and treatment of cancer. In this study, the three main compounds of curcuminoids-curcumin, desmethoxycurcumin, and bisdesmethoxycurcumin-were determined by reversed-phase high performance liquid chromatography (HPLC) to quantify total content in a mixture. Subsequently, the effect of the three curcuminoids, employed as one sample, was evaluated, to study the proliferation, apoptosis, cell cycle, and migration of the human ovarian cancer cell line SKOV-3. The results reveal that curcuminoids inhibit the proliferation of SKOV-3 cells with concentration-and time-dependent mechanisms. The morphological analysis of the treated SKOV-3 cells showed a typical apoptotic phenotype-cell shrinkage and membrane blebbing in a dose-dependent manner. In addition, flow cytometry demonstrated an increase in apoptosis with an IC 50 of 30 µM curcuminoids. The migration of SKOV-3 cells was also inhibited, reflected by a decrease in wound area. Furthermore, the curcuminoids were found to have no stimulation effect on the expression of cytokines TNF-α and IL-10. These results suggest that a curcuminoid mixture can effectively suppress epithelial cancer cell growth in vitro by inducing cellular changes and apoptosis.

This study was conducted as a trail to abrogates acrylamide induced hepatotoxicity in male rats by administration of copper (I) nicotinic acid complex. Animals were divided into 4 groups ;GI: control kept on balanced diet and tap water , GII: Acrylamide group received acrylamide in drinking water (7.5 mg/kg b.w.) for 30 days. GIII: treated with copper (I)-nicotinate complex (400 μg/kg b.w.) after acrylamide intoxication for 30 days and GIV the complex then acrylamide (prophylactic). Results showed significant increase in serum levels of AST, ALT, ALP, GGT and total antioxidant capacity (TAC) in acrylamide group. Moreover a significant increase in tumer markers AFU and TNF-Alpha. while Levels of each of S. total protein and S. albumin were significantly decreased in ACR group compared with control. Histological study showed congestion of central vein in liver section and vacuolation of hepatocytes in ACR group. Anticancer activity using in-vitro cytotoxic assay of Cu (I) Nicotinate complex ; proves the anticancer properties of it comparing with doxorubicin. Treatment with Copper (I)-Nicotinate Complex restored tissue and serological indices concomitantly towards normal levels. These results revealed that Copper (I)-Nicotinate Complex is able to significantly alleviate the hepatotoxicity induced by AA in rats and could be utilized as a potent food additives.