title: Progressive and concordant expression of PKC-eta and iNOS phenotypes in monocytes from patients with rheumatoid arthritis: association with disease severity.
abstract: Rheumatoid arthritis (RA) is a relatively common autoimmune disease with strong genetic and environmental determinants. The disease manifests itself as inflammation of the synovia and usually progresses to joint erosion and destruction. The disease can also be considered as a systemic disease because extra-articular manifestations are often observed throughout many organs and tissues of the body. Patients with severe RA have altered peripheral blood monocytes (PBM) that express activation markers. Two such markers, PKC-eta and iNOS, were studied using confocal laser scanning microscopy to determine how these markers are expressed during disease progression. Healthy individuals expressed neither of the two markers, but there was an elevated level of PKC-eta observed as the disease progressed (40% in mild RA and 100% in severe RA patients). Concordant expression of the two markers was observed in only 3% of PBM from mild RA patients, reaching 38% in severe RA patients. No cells expressing iNOS alone were observed in any of the patients studied. These data support the hypothesis linking PKC-eta expression with the regulation and predisposition to the development of the iNOS phenotype in severe RA patients. PKC-eta may therefore be a key regulator in the production of elevated plasma nitric oxide (NO) and corresponding circulating reactive nitrogen intermediates in severe RA and may be a possible target to regulate iNOS induction and NO production by monocytic cells in RA patients and possibly other inflammatory diseases.
authors.affiliation: Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.
authors.forename: Catherine Elizabeth
authors.initials: CE
authors.lastname: Heale
authors.forename: Goverdina Elisabeth
authors.initials: GE
authors.lastname: Fåhraeus-Van Ree
authors.forename: Proton
authors.initials: P
authors.lastname: Rahman
authors.forename: Vernon John
authors.initials: VJ
authors.lastname: Richardson
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology*; D009569:Nitric Oxide / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000097:blood; D055095:Optics and Photonics; D010641:Phenotype; D011493:Protein Kinase C / Q000096:biosynthesis* / Q000097:blood; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C081975:protein kinase C eta; D011493:Protein Kinase C