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  • Title: Elevated serum nitric oxide levels in patients with inflammatory arthritis associated with co-expression of inducible nitric oxide synthase and protein kinase C-eta in peripheral blood monocyte-derived macrophages.
    Author: Pham TN, Rahman P, Tobin YM, Khraishi MM, Hamilton SF, Alderdice C, Richardson VJ.
    Journal: J Rheumatol; 2003 Dec; 30(12):2529-34. PubMed ID: 14719189.
    Abstract:
    OBJECTIVE: To quantify circulating nitric oxide (NO) levels and inducible NO synthase (iNOS) expression in peripheral blood monocyte-derived macrophages (PB-MDM) from patients with inflammatory arthritis (IA) as a measure of disease activity, and to determine if there is a correlation between expression of iNOS and protein kinase C-eta (PKC-eta). 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-eta and iNOS was investigated by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. RESULTS: Serum NO (189.9 +/- 49.7 microM) was significantly higher (p < 0.0028) in IA patients than in controls (131.1 +/- 18.5 microM) or patients with OA (126.9 +/- 37.1 microM). 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-eta. 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-eta and iNOS expression in arthritis, supporting our earlier in vitro findings that PKC-eta expression was essential for lipopolysaccharide-mediated iNOS induction and NO production in human monocytes. PKC-eta may be important for the development of IA-induced iNOS positive phenotype in human PB-MDM.
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