Macrophages, human, nitric oxide production

We believe that the /3 cell is a source of nitric oxide production by human islets because (1) IL-1 and IFN-induced nitric oxide production by human macrophages has not been clearly demonstrated (2) the cytokine combination of IL-1, IFN, and TNF induces the formation of nitric oxide by human islets either freshly isolated or cultured for 7 days at 25°C (a procedure which removes 80-90% of nonendocrine cells from the islet) and also by islets cryoperserved and (3) NADPH—diaphorase staining reveals that approximately 60-70% of human islet cells treated with cytokines stain for NADPH-diaphorase (J. A. Corbett and M. L. McDaniel, unpublished data). TTiis staining procedure has been shown to colocalize with nitric oxide synthase in a number of cells including rat islets (Corbett et al., 1993c), and nitric oxide synthase has been demonstrated to contain NADPH-diaphorase enzymatic activity (Dawson et al., 1991 Hope et... 

Activated macrophages and microglia are likely cellular sources of IL-1 in the central nervous system. IL-la and p, both 17-kDa proteins, are the products of two distinct genes and produce many of the same effects that TNF has on glial cells. IL-1 upregulates cytokine production, includes cell surface molecules, activates nitric oxide, and stimulates proliferation. When used alone, IL-1 and TNFa both stimulate nitric oxide production in C6 cells. However, in human fetal astrocyte cultures, IL-1 is a better nitric oxide inducer when used in combination with IFNy. 

Two further perspectives on the use of tetracychnes in rheumatoid arthritis have been pubhshed (14,15). In addition to an effect on matrix metalloproteinases, the authors focused on a potential antiarthritic action of tetracyclines by their effects in the interaction between the generation of nitric oxide, matrix metalloproteinase release, and chondrocyte apoptosis. Both minocychne and doxycycline inhibit the production of nitric oxide from human cartilage and murine macrophages (16) in concentrations that are achieved in vivo. The authors suggested that tetracyclines may have several potential chondroprotective effects direct inhibition of matrix metalloproteinase activity and, by inhibition of nitric oxide production, further reduction of matrix metalloproteinase activity, reversal of reduced matrix synthesis, and reduced chondrocyte apoptosis. 

Weinberg, J.B., Misukonis, M.A., Shami, P.J., Mason, S.N., Sauls, D.L., Dittman, W.A., Wood, E.R., Smith, G.K., McDonald, B., Bachus, K.E., et al. (1995). Human mononuclear phagocyte inducible nitric oxide synthase (iNOS) analysis of iNOS mRNA, iNOS protein, biopterin, and nitric oxide production by blood monocyte and peritoneal macrophages. Blood 86,1184—1195. 

Recently, the possibility to use C60 as anti-inflammatory compound has been reported (Huang et al., 2008). Fullerene-xanthine hybrids have been studied to determine if nitric oxide (NO) and tumor necrosis factor-alpha (TNF-a) production in lipopolysaccharide (LPS)-activated macrophages can be inhibited by hybrid administration, finding positive results. The presence of xanthine moiety seems to be essential for the inhibition of LPS-induced TNF-a production, while the fullerene portion ameliorates the efficiency in LPS-induced NO production blockage, leading to a new promising class of potent anti-inflammatoiy agents. It is necessary to mention also the opposite results obtained by an amino acid fullerene derivative tested on human epidermal keratinocytes at concentration from 0.4 to 400 pg/mL. 

Compounds 44-56 from Alpinia blepharocalyx have all been shown to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine macrophages in vitro. Compound 55 was the most potent inhibitor [22]. Compounds 55 and 59 furthermore inhibited collagen-, arachidonic acid- and adenosine-induced platelet aggregation of human whole blood [26],... 

TABLE I Total Nitric Oxide (Micromolar) Production by Human Adult Blood Macrophages, Fetal Microglia, and Fetal Mixed Glial Cells... 

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