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

We have previously reported that granulocyte-macrophage colony-stimulating factor (GM-CSF) given after the administration of 5-fluorouracil (5-FU) results in augmented hematopoietic recovery as evidenced by increased white blood cell and neutrophil counts. Mice receiving GM-CSF following 5-FU administration were observed to have a marked elevation in splenic granulocyte-macrophage colony-forming cells (GM-CFC) and a decrease in the femoral bone marrow GM-CFC. Because GM-CSF has been shown to increase prostaglandin synthesis and prostaglandins are thought to provide a negative feedback signal to down-regulate myelopoiesis, we sought to determine if the cyclooxygenase inhibitor, indomethacin, could prevent the reduction in the number of femoral bone marrow GM-CFC seen when GM-CSF was administered following 5-FU. Groups of mice received a single 60 mg/kg i.p. injection of 5-FU followed 24 h later by twice-daily injections of 1 micrograms GM-CSF and daily injections of 3, 5, or 6 mg/kg indomethacin; the hematopoietic assays were performed on day 7 following 5-FU. Compared to those animals that received GM-CSF alone following 5-FU, mice receiving 5 mg/kg indomethacin plus GM-CSF following 5-FU had increased numbers of GM-CFC in their bone marrow (3923 +/- 634 vs 971 +/- 138; p less than 0.001) as well as increased neutrophil counts (18,995 +/- 2872 vs 11,497 +/- 2476; p less than 0.01). Indomethacin alone was, in part, capable of facilitating hematopoietic recovery following 5-FU administration, but not to the extent seen when used in combination with GM-CSF. Prostaglandin inhibitors may have a role in combination with hematopoietic growth factors in accelerating hematopoietic recovery following cytoreductive chemotherapy.
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PMID:Indomethacin augments granulocyte-macrophage colony-stimulating factor-induced hematopoiesis following 5-FU treatment. 220 40

We investigated the expression of peroxisome proliferator-activated receptors (PPAR) in human cultured mast cells (HCMC) by using the reverse transcription-polymerase chain reaction. HCMC expressed mRNA of PPARbeta, gamma1, and gamma2 constitutively, whereas PPARalpha was not detected. Though PPARgamma2 was expressed weakly, activation of HCMC with anti-IgE after IgE sensitization or with calcium ionophore plus phorbol ester resulted in increased expression of PPARgamma2 specifically. These stimuli did not influence the expression of PPARalpha and beta. In addition, provocation of HCMC with IgE or with IL-4 increased the mRNA level of PPARgamma2, and a synergistic effect was observed with the combination of IgE plus IL-4. To investigate a possible role of PPAR in mast cells, we examined the effects of PPAR agonists on cytokine production by HCMC. Prostaglandin (PG) D(2), Delta(12)-PGJ(2), 15deoxy-Delta(12, 14)-PGJ(2) (15d-PGJ(2)), and troglitazone, all of which are PPARgamma agonists, attenuated the production of granulocyte-macrophage colony-stimulating factor by anti-IgE-stimulated HCMC. A similar effect was observed with carbaprostacyclin, a PPARbeta agonist, but not with PPARalpha agonists. Anti-IgE-induced expression of cytokine mRNA, such as TNF-alpha, IL-5 and macrophage inflammatory protein-1alpha mRNA, was also reduced by the treatment with these PPARgamma agonists. Though only Delta(12)-PGJ(2) and 15d-PGJ(2) revealed an inhibitory effect on histamine release, leukotriene C(4) release from HCMC was suppressed by all tested PPARgamma agonists. These results indicate that HCMC express PPARbeta and gamma1/2, which might negatively regulate the activation of HCMC.
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PMID:Peroxisome proliferator-activated receptors are expressed in human cultured mast cells: a possible role of these receptors in negative regulation of mast cell activation. 1109 53