In addition to chemotaxis, and by signalling through the receptor ChemR23, the isoforms produced by serine proteases possess pro inflammatory properties, whereas those gen erated by cysteine proteases exert anti inflammatory activities. Accordingly, prochemerin appears to mediate dual effects, depending on the type of chemerin isoform produced. The receptor ChemR23, also known as chemokine like receptor 1, is expressed primarily by profes sional antigen presenting cells such as dendritic cells. natural killer cells and macrophages. Hence, it is a leukocyte chemoattractant receptor which directs the migration of these cells to sites of inflamma tion.
Neutrophils, the predominant leukocytes present during early acute inflammation, are capable of promot ing maturation of prochemerin to IPI-145 ic50 chemerin, thus sug gesting that the chemerinChemR23 signalling system may serve as a bridge between innate and adaptive immunity, as shown by the fact that ChemR23 is expressed by both myeloid DCs and plasmacytoid DCs, subsequently promoting adaptive immunity. There is compelling evidence of beneficial effects of dietary supplements of eicosapentaenoic acid in a wide range of human inflammatory conditions including arthritis. The mechanisms explaining the benefi cial effects of EPA is still debated, and the primary the ory is that EPA interferes with the oxidation of aracidonic acid, by competitive inhibition. It has also been suggested that 15 lipoxygenase products of EPA can affect the transcription factor NF B, pre venting the activation of inflammatory genes.
One interesting finding is that ChemR23 binds the endogenous lipid mediator derived from EPA, resolvin E1, that in leukocytes leads to anti inflammatory signalling and promotion selleck chemical MLN2480 of resolution. In the present study we aimed to clarify whether human articular chondrocytes express ChemR23 and whether recombinant chemerin21 157 could elicit inflam matory signalling in these cells. Moreover, cellular expression of chemerin was investigated to unravel a possible inflammatory circuit in joints which may be exploited by lipidmediators derived from EPA to pro mote resolution. Materials and methods The experiments were performed in accordance with The Code of Ethics of the World Medical Association for experiments involving humans. Patients gave a written informed consent to use biopsies for scientific purposes, and the project was approved by The Regional Ethics Committee.
Acquisition of chondrocytes Human articular chondrocytes from knee joints were obtained from patients subjected to autologous chon drocyte transplantation and from osteoarthritic patients subjected to total knee arthroplasty. Biop sies from ACT patients were collected and prepared as previously described, while biopsies from osteoar thritic joints were taken from areas macroscopically judged as the healthiest part of the cartilage.