Simvastatin acts as an inhibitor of interferon gamma-induced cycloxygenase-2 expression in human THP-1 cells, but not in murine RAW264.7 cell

Cyclooxygenase-2 (COX-2) is a key inflammatory response molecule, and associated with many immune functions of monocytes/macrophages. Particularly, interferon gamma (IFNgamma)-induced COX-2 expression appears in inflammatory conditions such as viral infection and autoimmune diseases. Recently, statins have been reported to show variable effects on COX-2 expression, and on their cell and species type dependences. Based on the above description, we compared the effect of simvastatin on IFNgamma-induced COX-2 expression in human monocytes versus murine macrophages. In a result, we found that simvastatin suppresses IFNgamma-induced COX-2 expression in human THP-1 monocytes, but rather, potentiates IFNgamma-induced COX-2 expression in murine RAW264.7 macrophages. However, signal transducer and activator of transcriptio n 1/3 (STAT1/3), known as a transcription factor on COX-2 expression, is inactivated by simvastatin in both cells. Our findings showed that simvastatin is likely to suppress IFNgamma-induced COX-2 expression by inhibiting STAT1/3 activation in human THP-1 cells, but not in murine RAW264.7 cells. Thus, we concluded that IFNgamma-induced COX-2 expression is differently regulated by simvastatin depending on species specific mechanism.

Superoxide release and cellular gluthatione peroxidase activity in leukocytes from children with persistent asthma

Asthma is an inflammatory condition characterized by the involvement of several mediators, including reactive oxygen species. The aim of the present study was to investigate the superoxide release and cellular glutathione peroxidase (cGPx) activity in peripheral blood granulocytes and monocytes from children and adolescents with atopic asthma. Forty-four patients were selected and classified as having intermittent or persistent asthma (mild, moderate or severe). The spontaneous or phorbol myristate acetate (PMA, 30 nM)-induced superoxide release by granulocytes and monocytes was determined at 0, 5, 15, and 25 min. cGPx activity was assayed spectrophotometrically. The spontaneous superoxide release by granulocytes from patients with mild (N = 15), moderate (N = 12) or severe (N = 6) asthma was higher at 25 min compared to healthy individuals (N = 28, P < 0.05, Duncan test). The PMA-induced superoxide release by granulocytes from patients with moderate (N = 12) or severe (N = 6) asthma was higher at 15 and 25 min compared to healthy individuals (N = 28, P < 0.05 in both times of incubation, Duncan test). The spontaneous or PMA-induced superoxide release by monocytes from asthmatic patients was similar to healthy individuals (P > 0.05 in all times of incubation, Duncan test). cGPx activity of granulocytes and monocytes from patients with persistent asthma (N = 20) was also similar to healthy individuals (N = 10, P > 0.05, Kruskal-Wallis test). We conclude that, under specific circumstances, granulocytes from children with persistent asthma present a higher respiratory burst activity compared to healthy individuals. These findings indicate a risk of oxidative stress, phagocyte auto-oxidation, and the subsequent release of intracellular toxic oxidants and enzymes, leading to additional inflammation and lung damage in asthmatic children.

Insulin receptor tyrosine kinase activity in monocytes of type 2 diabetes mellitus patients receiving oral L-lysine.

The action of lysine as an antidiabetic agent was examined in human volunteers. Eight patients with type 2 DM were orally supplemented with L-lysine hydrochloride 1 g/day in two doses along with antidiabetic tablets (glyciphage or chlorformine), for a period of two months. Periodically their plasma fasting sugar and insulin receptor tyrosine kinase activity was measured in their monocytes. Eight normal healthy volunteers served as controls for comparison of receptor tyrosine kinase activity. Insulin receptor tyrosine kinase was isolated from monocytes by immunoprecipitation and the activity was determined using exogenous substrate poly glu-tyr (4:1) and radioactive ATP. Phosphorylated peptide was separated by electrophoresis and quantified using a liquid scintillation system. The enzyme activity was significantly low (22074 +/- 1728 dpm/ml immunoprecipitate) in subjects with diabetes when compared to non-diabetic control group (50,775 +/- 3597). Lysine treatment enhanced the enzyme activity by 31% in patients with diabetes and decreased their blood sugar by 27%.

Fosfatasa acida leucocitaria tartrato resistentecomo marcador de la transformacion del monocito en macrofago / Leucocyte tartrate-resistant acid phosphatase as marker for the transition of monocyte to macrophage

Se investigó la presencia de la 5 isoenzima de la fosfatasa ácida leucocitaria tartrato resistente (FATRE) en los monocitos de sangre periférica humana en 32 muestras: 26 normales, 4 plaquetopenias, 1 anemia y 1 tricoleucemia. Se empleó el separador celular Cobe Spectra Versión 4 en 3 muestras y en las demás se obtuvo la concentración celular por centrifugación sin y con partículas de látex, para estudiar monocitos y macrófagos, respectivamente. Empleando el Kit Sigma para las dos reacciones de fosfatasa ácida total y de FATRE, se demostró la presencia de dos poblaciones de monocitos, una minoritaria para FATRE y otra negativa. Con la adición de látex los monocitos se transformaron en macrófagos haciéndose fuertemente positivos para FATRE. En consecuencia se concluye que la FATRE debe desempeñar un papel principal en la función macrofágica y por ende en la inmunidad celular humana.

Alpha-naphthyle acetate esterase activity in monocytes and lymphocytes of normal and muscular dystrophic individuals

The cytochemical reaction for [Alpha] -naphthyl acetate esterases in monocytes and lymphocytes of normals and patients with Duchenne, limb-girdle and facios-capulohumeral muscular dystrophies, was studied. A-, B- and choline esterases were the main esterases of normal monocytes and lymphocytes. The latter contained C-esterase in addition. Deranged pattern of esterase activity and deficient A-esterase activity was found in muscular dystrophy. The above findings are discussed and comments are put forward in the direction of finding clue[s] for the nature of the dystrophic defect