Heparan/chondroitin/dermatan sulfate primer 2-(6-hydroxynaphthyl)-O-beta-D-xylopyranoside preferentially inhibits growth of transformed cells |
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Authors: | K Mani B Havsmark S Persson Y Kaneda H Yamamoto K Sakurai S Ashikari H Habuchi S Suzuki K Kimata A Malmstr?m G Westergren-Thorsson LA Fransson |
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Affiliation: | Third Division of Internal Medicine, IRCCS Ospedale Maggiore, Milano, Italy. Anna.Catania@unimi.it |
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Abstract: | Melanocortins are proopiomelanocortin-derived peptides that include adrenocorticotropic hormone ACTH (1-39)], alpha-melanocyte-stimulating hormone alpha-MSH (1-13)], and related amino acid sequences. Melanocortin peptides have potent antiinflammatory/anticytokine activity. Because cytokines such as interleukin 1 (IL-1) and tumor necrosis factor (TNF) can be detrimental in HIV-infected patients, we investigated the effects of melanocortins on production of IL-1 and TNF alpha in the blood of HIV patients. Cytokine production was measured in whole blood samples stimulated with LPS in the presence or absence of alpha-MSH (1-13), alpha-MSH (11-13), ACTH (1-24), or ACTH (1-39). Melanocortins reduced production of both cytokines in a concentration-dependent fashion. In separate experiments on normal peripheral blood mononuclear cells (PBMC), alpha-MSH (1-13) inhibited production of IL-1 beta and TNF alpha induced by HIV envelope glycoprotein gp 120. These results suggest that stimulation of melanocortin receptors in inflammatory cells could be a novel way to reduce production of cytokines that promote HIV replication. |
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