Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have reported that melatonin may rescue bone marrow cells from apoptosis induced either in vivo or in vitro by cancer chemotherapy compounds via bone marrow T-cells and endogenous release of granulocyte-macrophage colony-stimulating factor. Here we show that the number of granulocyte/macrophage colony-forming units cultured with suboptimal concentrations of colony-stimulating factor was higher in the presence of melatonin both at physiological and pharmacological concentrations. CD4+,Thy-1.2+ cell depletion or addition of anti-mouse interleukin 4 monoclonal antibodies prevented both effects of melatonin. Upon incubation with etoposide, the concentration of myeloid precursors was 43 +/- 8 per 10(5) cells. The melatonin+etoposide value was 68 +/- 7, whereas that of melatonin+etoposide+anti-interleukin 4 was 38 +/- 6. Melatonin was also ineffective when bone marrow cells were separated in adherent and nonadherent populations. Supernatants from nonadherent cells incubated with melatonin proved to contain interleukin 4 activity which, however, showed its influence on unseparated bone marrow and adherent cells but not on nonadherent cells. It is proposed that melatonin represents a neuroendocrine regulator of interleukin 4 production in bone marrow T-helper cells. Interleukin 4 may then stimulate adherent stromal cells to produce granulocyte/macrophage colony-stimulating factor. Such a neuroendocrine-cytokine mechanism may explain the hematopoietic rescue of melatonin as well as its antitumoral and immunoenhancing properties.
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PMID:Colony-stimulating activity and hematopoietic rescue from cancer chemotherapy compounds are induced by melatonin via endogenous interleukin 4. 791 29

Male albino mice immunodepressed after the injection of dexamethasone (DEX) were inoculated intraperitoneally with the Guajira strain of Venezuelan equine encephalomyelitis (VEE) virus. Melatonin (MLT) was administered daily, at a dose of 500 micrograms/kg bodyweight, for 3 days before virus inoculation and 10 days after. Serum levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) were determined in all the experimental groups (control, DEX, DEX + MLT, DEX + VEE, DEX + VEE + MLT, VEE and MLT). At day 6 after the virus inoculation, the survival rate was significantly increased from 0% in group DEX + VEE to 32.5% in the group of immunodepressed infected mice treated with MLT (DEX + VEE + MLT). By day 10 a survival rate of 10% was found in group DEX + VEE + MLT and 0% in group VEE. No alterations in IL-2 serum levels were observed. MLT increased GM-CSF in control and in DEX-treated mice. In the VEE virus-infected mice treated with DEX, serum levels of GM-CSF increased progressively from day 1 to 5 postinoculation. In contrast, the levels of GM-CSF in infected immunodepressed mice treated with MLT decreased significantly from day 1 to 5 postinoculation. At day 5 after viral inoculation, no differences were detected in the cerebral viral titres in groups VEE, DEX + VEE and DEX + MLT + VEE. These results show that MLT does not inhibit VEE viral replication in the brain of immunodepressed mice.
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PMID:Melatonin prolongs survival of immunodepressed mice infected with the Venezuelan equine encephalomyelitis virus. 1135 63

It is hypothesized that, besides increased free radical production, aging is a process also related to inflammation. Thus, female and male senescence-accelerated (SAMP8) and senescence-resistant (SAMR1) mice of 5 and 10 months of age were studied to assess this hypothesis. Plasma from these mice was processed to determine nitric oxide (NO), and pro-inflammatory [interleukin (IL)-1beta, IL-2, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and granulocyte-macrophage colony-stimulating factor] and anti-inflammatory (IL-4, IL-5 and IL-10) cytokines. The results show the presence of an age-dependent increase in IFN-gamma and TNF-alpha and a reduction in IL-2 levels, with minor changes in the remaining cytokines. Moreover, age was associated with a significant increase in NO levels. Chronic melatonin administration between 1 and 10 months of age counteracted the age-dependent production of pro-inflammatory cytokines and NO, reducing them to the levels found at 5 months of age. Melatonin also reduced the levels of the anti-inflammatory cytokines. The results of this study suggest the existence of an inflammatory process during aging and further support that melatonin behaves as an essential molecule against aging, for its anti-inflammatory properties together with its antioxidative role reported elsewhere.
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PMID:Chronic melatonin treatment reduces the age-dependent inflammatory process in senescence-accelerated mice. 1734 26