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Elevated Serum Nitric Oxide Levels in Patients with Inflammatory Arthritis Associated with Co-expression of Inducible Nitric Oxide Synthase and Protein Kinase C-h in Peripheral Blood Monocyte-Derived Macrophages
TRAM N.Q. PHAM, PROTON RAHMAN, YVONNE M. TOBIN, MAJED M. KHRAISHI, SEAN F. HAMILTON, CATHERINE ALDERDICE, and VERNON J. RICHARDSON
ABSTRACT.
Methods. PB-MDM were isolated from whole blood of 20 patients with IA (14 rheumatoid arthritis and 6 peripheral spondyloarthropathies). Thirteen patients with osteoarthritis (OA) and 9 healthy individuals were controls. Serum NO levels were measured by indirect determination of nitrite and nitrate. Expression of PKC-h and iNOS was investigated by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Results. Serum NO (189.9 ± 49.7 µM) was significantly higher (p < 0.0028) in IA patients than in controls (131.1 ± 18.5 µM) or patients with OA (126.9 ± 37.1 µM). IA patients with severe inflammation had highest levels of NO, while those with mild inflammation had normal levels of NO. RT-PCR showed that PB-MDM from IA patients with active disease co-expressed iNOS and PKC-h. This was observed in 15 out of 16 cases. All other groups with normal plasma NO expressed neither gene. Conclusion. Our findings show that elevated plasma NO levels were only present in IA patients with severe disease activity. We show for the first time a positive correlation between PKC-h and iNOS expression in arthritis, supporting our earlier in vitro findings that PKC-h expression was essential for lipopolysaccharide-mediated iNOS induction and NO production in human monocytes. PKC-h may be important for the development of IA-induced iNOS positive phenotype in human PB-MDM. (J Rheumatol 2003;30:2529-34) Key Indexing Terms:
NITRIC OXIDE
From the Faculty of Medicine, Memorial University of Newfoundland and Rheumatology Research, St. Clare's Mercy Hospital, St. John's, Newfoundland, Canada. Supported by the Faculty of Medicine, Memorial University of Newfoundland. T. Pham, BSc, PhD candidate, Memorial University of Newfoundland; P. Rahman, MD, FRCPC; Y. Tobin, RN; M. Khraishi, MD, FRCPC; S. Hamilton, MD, FRCPC; C. Alderdice, MD, FRCPC, St. Clare's Mercy Hospital; V. Richardson, PhD, Associate Professor, Divisions of Surgery and Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland. Address reprint requests to Dr. V. Richardson, Divisions of Surgery and Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland A1B 3V6, Canada. E-mail: vrichard@mun.ca Submitted November 8, 2002; revision accepted May 13, 2003. |