Introduction Phosphatidylcholine and phosphatidylcholine-derived metabolites exhibit anti-inflammatory properties in various stress conditions. of cannabinoid receptors 1 and 2, TNF and 685898-44-6 supplier endothelial and inducible nitric oxide synthase were determined, and classical histological analysis was performed. Results Phosphatidylcholine pretreatment reduced the collagen-induced arthritis-induced hypersensitivity, and decreased the number of leukocyteCendothelial cell interactions and the extent of functional capillary density as compared with those of group 1. It also ameliorated the tissue damage and decreased inducible nitric oxide synthase expression. The expressions of the cannabinoid receptors and TNF were not influenced by the phosphatidylcholine intake. Phosphatidylcholine-enriched food administrated as therapy failed to evoke the aforementioned changes, apart from the reduction of the inducible nitric oxide synthase expression. Conclusions Phosphatidylcholine-enriched food as pretreatment, but not as therapy, appears to exert beneficial effects on the morphological, functional and microcirculatory characteristics of chronic arthritis. We propose that oral phosphatidylcholine may be a preventive approach in ameliorating experimental rheumatoid arthritis-induced joint damage. Introduction Rheumatoid arthritis (RA) reduces the health-related quality of life and imposes a substantial burden on both the individual and society . The generalized chronic inflammation profoundly affects the function of several organ systems  and leads to symmetric, erosive skeletal changes, especially in the minor joints. Although the pathomechanism is still unclear, a number of data suggest that inflammatory mediators from the synovium play central roles in secondary structural bone damage [3,4]. By means of intravital microscopy (IVM), it has been shown that the granulocytes are the first major cell population recruited to the inflamed joints during the early phase of experimental RA . The ensuing tissue destruction can be ascribed, at least partly, to leukocyte extravasation and the interference of activated synovial polymorphonuclear (PMN) granulocytes with other infiltrating immune cells and their products. Many different disease-modifying antirheumatic drugs have been used to date, but the shaping of optimal therapy is difficult C mainly due to the prolonged application, side effects and costs of different agents [6,7]. In this respect, targeted nutritional interventions have 685898-44-6 supplier many advantages, and various experimental and clinical data have indicated that dietary phosphatidylcholine (PC) may potentially function as an anti-inflammatory substance [8-11]. PC, a ubiquitous component of biological membranes, has additionally been demonstrated to increase the tissue tolerance in experimental models of ischemia and hypoxia [12-14]. The notion that PC may be anti-inflammatory is supported by the finding that PC metabolites with an alcoholic moiety in the molecule (choline, N,N-dimethylethanolamine and N-methylethanolamine) inhibit the reactive oxygen species-producing activity of isolated PMN granulocytes . On the above basis, we hypothesized that exogenous PC may influence the evolution of inflammatory reaction in collagen-induced arthritis (CIA), a major murine model of RA [16,17]. Our primary aim was to explore the consequences of dietary PC supplementation on certain in vivo inflammatory parameters. To this end, we characterized the leukocyteCendothelial cell interactions and perfusion characteristics in the synovial microcirculation , and compared the effectiveness of oral PC pretreatment with that of PC therapy when the treatment protocol 685898-44-6 supplier was initiated only after the occurrence of signs of inflammatory disease. The study additionally extended to the effects of PC supplementation on endogenous cannabinoid receptor activation in the synovia. TNF, endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) expression levels were chosen as further endpoints to characterize the modulation of the anti-inflammatory potential of the nutrition protocols. Materials and methods Animal model The experiments were performed on 50 male DBA1/J mice kept under specified pathogen-free conditions in isolated ventilated cages with a 12-hour light/dark cycle. The experimental protocol was approved by the local animal rights protection authorities and followed the National Institutes of Health guidelines for the care and use of laboratory animals. At the age of 685898-44-6 supplier 8 weeks, mice were immunized intradermally at the base of the tail with 50 l bovine collagen II (2.5 mg/ml (Chondrex, Redmond, WA, USA) emulsified in 50 l complete Freund’s adjuvant (CFA) (4 mg/ml,; DIFCO, Detroit, MI, Mouse monoclonal to ALCAM USA) in order to induce CIA (groups 1 to 3), or received CFA only (control groups 4 and 5). A second, booster immunization was performed 3 weeks later, when 50 l incomplete Freund’s adjuvant was administered with or without the same volume of collagen II. The animals were randomly allocated into the experimental groups. In group 1 (n = 10), the animals were immunized with collagen II in CFA, and were then kept on water and standard laboratory chow ad libitum (Ssniff Spezialdi?ten GmbH, Soest, Germany). The mice were observed for 6 weeks after the first immunization. The animals in group 2 (PCpre, n =.