ABSTRACT
TNF-alpha is a major cytokine involved in inflammatory bowel disease (IBD). In this study, water extract of Grifola frondosa (GFW) was evaluated for its protective effects against colon inflammation through the modulation of TNF-alpha action. In coculture of HT-29 human colon cancer cells with U937 human monocytic cells, TNF-alpha-induced monocyte adhesion to HT-29 cells was significantly suppressed by GFW (10, 50, 100 microg/ml). The reduced adhesion by GFW correlated with the suppressed expression of MCP-1 and IL-8, the major IBD-associated chemokines. In addition, treatment with GFW significantly suppressed TNF-alpha-induced reactive oxygen species production and NF-kappaB transcriptional activity in HT-29 cells. In differentiated U937 monocytic cells, LPS-induced TNF-alpha production, which is known to be mediated through NF-kappaB activation, was significantly suppressed by GFW. In an in vivo rat model of IBD, oral administration of GFW for 5 days (1 g/kg per day) significantly inhibited the trinitrobenzene sulfonic acid (TNBS)-induced weight loss, colon ulceration, myeloperoxidase activity, and TNF-alpha expression in the colon tissue. Moreover, the effect of GFW was similar to that of intra-peritoneal injection of 5-aminosalicylic acid (5-ASA), an active metabolite of sulfasalazine, commonly used drug for the treatment of IBD. The results suggest that GFW ameliorates colon inflammation by suppressing production of TNF-alpha as well as its signaling through NF-kappaB leading to the expression of inflammatory chemokines, MCP-1 and IL-8. Taken together, the results strongly suggest GFW is a valuable medicinal food for IBD treatment, and thus may be used as an alternative medicine for IBD.
Subject(s)
Animals , Humans , Rats , Cell Adhesion/drug effects , Cell Extracts/administration & dosage , Chemokine CCL2/biosynthesis , Coculture Techniques , Colon/drug effects , Grifola , HT29 Cells , Inflammatory Bowel Diseases/chemically induced , Interleukin-8/biosynthesis , Intestinal Mucosa/drug effects , Monocytes/drug effects , NF-kappa B/genetics , Peroxidase/metabolism , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Stomach Ulcer , Transcription, Genetic/drug effects , Trinitrobenzenesulfonic Acid/administration & dosage , Tumor Necrosis Factor-alpha/biosynthesis , U937 Cells , Weight LossABSTRACT
MMR is a live attenuated vaccine. Indian children show almost 90% seroconversion against measles and rubella and 90% against mumps. Several adverse effects have been reported. Epidemiological studies do not support a causative link between MMR and autism, IBD or GBS. There is an association between the Urabe strain of mumps vaccine and viral meningitis. Vaccine associated thrombocytopenia has been reported. Severe hypersensitivity reactions occur, mainly due to the gelatin component. Outbreaks of measles occur in areas of high measles vaccine coverage, when susceptible individuals accumulate. A second dose is given mainly to vaccinate those who missed the first dose or had primary vaccine failure, rather than to boost waning antibody levels. The possibility or eradication of mumps with a second dose of mumps vaccine is being considered.