Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The usefulness of in situ hybridization for detecting mRNA encoding various kinds of proteins in megakaryocytic cell lines (K562, HEL and CMK) was examined. Using in situ hybridization, glycoprotein (GP) IIIa mRNA was found to be present in K562, HEL and CMK cells. Both GPIb and GPIIb mRNA were also present in HEL and CMK cells, while only HEL cells expressed platelet factor 4 mRNA. These findings were identical to those obtained with Northern blotting. It should be emphasized that in situ hybridization was useful to clearly define each cell expressing platelet specific protein mRNA. The expression of interleukin-6 (IL-6) and IL-6 receptor mRNA in mononuclear cells prepared from bone marrow aspirates was examined. In situ hybridization study demonstrated the presence of IL-6 receptor mRNA in the recognized megakaryocytes only, while IL-6 mRNA was found to be present in the megakaryocytes and a few mononuclear cells. These findings suggest that differentiation and proliferation of normal megakaryocytes might be controlled by an IL-6 autocrine loop, and detection of IL-6 receptor mRNA might be useful to identify megakaryocytes.
 ...
PMID:[Detection of mRNA in megakaryocytes using in situ hybridization]. 140 57

Data concerning megakaryocytopoiesis and its regulation were summarized in this report. Critical analysis of these data indicates that: (i) megakaryocytopoiesis is a complex, multiple-stage cellular and biologic process; (ii) the survival, proliferation and differentiation of progenitor cells into immature megakaryocytes are regulated mainly by interleukin-3, granulocyte-macrophage colony-stimulating factor and an as yet uncharacterized megakaryocyte colony-stimulating factor, and the maturation of immature megakaryocytes to produce platelets is regulated primarily by interleukin-6 and thrombopoietin; (iii) optimal megakaryocyte development needs adequate interactions of several growth factors with target cell population and hematopoietic microenvironment; (iv) megakaryocytopoietic inhibition is controlled essentially by megakaryocyte-platelet products such as transforming growth factor-beta, and platelet factor 4 and its related proteins; interferon-alpha and -gamma also are able to play an inhibitory role; and (v) expansion or decrease of either normal or neoplastic megakaryocyte progenitor cells, change of platelet mass and abnormalities of growth factor levels in hematopoietic tissue might result in an abnormal megakaryocytopoiesis.
 ...
PMID:Megakaryocytopoiesis: characterization and regulation in normal and pathologic states. 195 49

Megakaryocytopoiesis is a complex, highly regulated cellular and biologic process which leads to the production of platelets. The proliferation of megakaryocyte (MK) progenitors is mainly regulated by interleukin-3, granulocyte-macrophage colony-stimulating factor and an as yet uncharacterized MK colony-stimulating factor. The maturation of MKs to produce platelets is essentially regulated by interleukin-6 and thrombopoietin. Optimal megakaryocytopoiesis is controlled by appropriate combinations of positive and negative influence. Megakaryocytopoietic inhibition is controlled by transforming growth factor beta, platelet factor 4 and its related proteins, interferon-alpha and -gamma.
 ...
PMID:Regulation of human megakaryocytopoiesis. 210 71

Both normal and leukaemic human megakaryocytopoiesis are stimulated by several cytokines, including stem cell factor, granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-3, GM-CSF/interleukin-3 fusion protein, interleukin-6, interleukin-11, basic fibroblast growth factor and thrombopoietin, but are inhibited by tumour necrosis factor-alpha, platelet factor 4, beta-thromboglobulin, thrombin, interleukin-4, interferon-alpha and interferon-gamma. Human megakaryoblastic leukaemia cell lines have common biological features, including high expression of the megakaryocytic specific antigen: CD41; high expression of the early myeloid antigens: CD34 and CD33; constitutive expression of interleukin-6 and platelet-derived growth factor; complex karyotype picture; expression of c-kit: the stem cell factor receptor; growth-dependency or -stimulation by stem cell factor, interleukin-3 and/or GM-CSF; megakaryoblastic differentiation by phorbol-myristate-acetate; and in vivo tumorigenicity in mice is associated with marked fibrosis. Only a few agents including phorbol-myristate-acetate; vitamin D3, interferon-alpha, interferon-beta 2, erythropoietin and thrombin have been reported to induce megakaryocytic differentiation in the human megakaryoblastic leukaemia cells.
 ...
PMID:Characteristic biological features of human megakaryoblastic leukaemia cell lines. 756 68

We have established a novel human megakaryoblastic cell line, designated as MEG-A2, from a patient with megakaryoblastic crisis of Philadelphia (Ph) chromosome positive chronic myelogenous leukemia. MEG-A2 cells showed positive phenotypes for periodic acid Schiff and alpha-naphthylbutyrate esterase reactions, but were negative for myeloperoxidase and naphthol ASD chloroacetate esterase reactions. Flow cytometric analyses of cell surface markers revealed that MEG-A2 cells had a low level of GP IIb/IIIa expression as well as apparent expressions of CD4, CD7, CD13, CD33 and CD34 antigens, but no expression of GP Ib nor glycophorin A. Stimulation with phorbol 12-myristate 13-acetate (PMA) dramatically increased the expression of megakaryocyte-related markers such as HPL-3, J15, Pit-1, Y2/51 and AN51 in MEG-A2 cells. The PMA-stimulation also induced expression of platelet peroxidase (PPO) in MEG-A2 cells on electromicroscopic observation. Proliferative responses to granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) or erythropoietin were observed, and the expression of GP IIb/IIIa was increased by stimulation with GM-CSF, IL-3, erythropoietin and interleukin-6 (IL-6). Protein S mRNA expression was seen in cultured cells on Northern blot analysis. Expression of platelet factor 4 mRNA was induced in PMA-stimulated cells, and a marked accumulation of protein was observed in the culture medium. In conclusion, a new cell line, MEG-A2, belongs to the relatively immature megakaryocytic lineage and has markedly increased megakaryocytic characteristics with PMA stimulation.
 ...
PMID:Establishment and characterization of an immature human megakaryoblastic cell line, MEG-A2. 786 73

It is known that platelet alpha-granule constituents including platelet-derived growth factor (PDGF), platelet factor 4 (PF4) and transforming growth factor-beta (TGF-beta) can affect megakaryocytopoiesis. Serotonin, a platelet dense granule constituent has been shown to have a mitogenic effect on fibroblasts and smooth muscle cells but whether it has the same effect on megakaryocytes remains unclear. In this study, we investigated the effect of serotonin on megakaryocytopoiesis and the possible mechanism of its effect using the mouse plasma clot culture method. The results show that: (a) serotonin significantly stimulates megakaryocyte colony formation with maximum stimulation at 100 nM; (b) enhanced action is found between serotonin and interleukin-3 (IL-3), interleukin-6 (IL-6), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin (EPO) and PDGF; (c) ketanserin, a 5-HT2 receptor antagonist, blocks the mitogenic effect of serotonin on megakaryocytopoiesis; and (d) Meg-01 cells (a megakaryocyte cell line) express 5-HT2 receptors. This study demonstrates that serotonin has a mitogenic effect on megakaryocytopoiesis and this effect may be mediated via the 5-HT2 receptor which is known to be coupled to G protein. It is suggested that serotonin may also be involved in the feedback control of megakaryocytopoiesis.
 ...
PMID:Serotonin stimulates megakaryocytopoiesis via the 5-HT2 receptor. 873 1

A new factor-independent megakaryoblastic cell line, designated SET-2, was established from the peripheral blood of a patient with leukemic transformation of essential thrombocythemia (ET). SET-2 expressed CD 4, 7, 13, 33, 34, 36, 38, 41, 61, 71, 117, 126, 130 and c-mpl. In addition, it spontaneously produced numerous platelet-like particles in liquid culture. These particles were shown to be the same size as normal platelets, and to express CD 36, 38, 41, 61 and 71. Proliferation of SET-2 was not influenced by thrombopoietin (TPO) and other hemopoietic cytokines. SET-2 was found to express the platelet-specific proteins such as platelet factor 4 and beta-thromboglobulin. The levels of expression were not altered by TPO. SET-2 also secreted interleukin-6 into the supernatants, as well as normal megakaryocytes. These results suggest that SET-2 spontaneously matures to megakaryocytes and produces platelet-like particles. These findings indicate that SET-2 may be useful for investigating the proliferation and differentiation mechanisms of leukemia cells and the role of c-mpl on megakaryoblasts, megakaryocytes, and platelets in ET. Leukemia (2000) 14, 142-152.
 ...
PMID:Establishment and characterization of a new human megakaryoblastic cell line (SET-2) that spontaneously matures to megakaryocytes and produces platelet-like particles. 1063 90

Systemic inflammation and the activation of the coagulation system following cardiopulmonary bypass (CPB) may contribute to postoperative complications. In vitro studies have demonstrated that heparin possesses anti-inflammatory properties. To ascertain the relative benefits of high versus low heparin doses, we studied the impact of varying heparin doses on the inflammatory response and coagulation system during and following CPB. Forty patients scheduled for elective coronary artery bypass surgery requiring CPB were randomized to either a low dose (300 U/kg) (Group L) or a high dose of unfractionated heparin (600 U/kg) (Group H). To evaluate the inflammatory response, proinflammatory cytokines [tumor necrosis factor-alpha and interleukin-6 (IL-6)] were measured at four different times: before CPB (T0), 30 min after the institution of CPB (T1), 30 min after cross-clamp release (T2), and 4 h after the end of CPB (T3). Thrombin-antithrombin complex, platelet factor 4 and anti-activated factor X heparin concentrations were also measured. Patients in Group H received greater heparin (44.934 U versus 27.741 U, P<0.001) and protamine (P=0.003) doses. Postoperative blood loss and blood products transfusions were not significantly different in the groups. At T1, mean heparin plasma concentration was higher in Group H (P<0.001). IL-6 was significantly lower in Group H compared with Group L (P=0.01) only at T1. Using a mixed-effects statistical model, tumor necrosis factor-alpha and IL-6 levels were comparable regardless of the heparin dose. Thrombin-antithrombin complex levels were lower in Group H (P=0.04) and platelet factor 4 levels were significantly lower in Group H at T2 (P=0.04). Higher heparin doses were associated with higher heparin concentrations during CPB. A high heparin dose achieved a better preservation of the coagulation system with less thrombin formation and platelet activation. The heparin dose had small influence on proinflammatory cytokines release.
 ...
PMID:The effects of high-dose heparin on inflammatory and coagulation parameters following cardiopulmonary bypass. 1597 Jul 15

We aimed to investigate whether atorvastatin influenced the CD40-CD40L pathway in atherosclerosis formation in rats fed a high cholesterol diet. Thirty-six male Wistar rats were divided among 4 groups as follows: control (C), statin (S), 5% cholesterol fed (HC), and statin-administered hypercholesterolemic (HCS). Serum levels of lipids, soluble CD40L, platelet factor 4, and interleukin-6 were assayed with commercial kits. The number of platelets expressing surface P-selectin, CD40, and CD40L were determined by flow cytometry. Aortas were examined for fatty streaks. In the HC group, we observed a significant increase in serum lipid levels and platelet activation markers compared with the control group. Rats in the HCS group had a significant decrease in lipid levels and downregulation in the number of platelets expressing surface P-selectin, CD40, and CD40L compared with the HC group. We observed decreased fatty streak formations in aortas in HCS rats. A positive correlation was found for platelet activation markers and atherosclerotic fatty streak formations. Regression analysis revealed that the predictor of atherosclerosis was CD40L. Our study suggests that in a rat hypercholesterolemic model, statin treatment may influence the CD40-CD40L dyad, and that this effect is parallelled by a suppression of progression of atherosclerotic plaque formation.
...
PMID:Effect of atorvastatin on atherosclerotic plaque formation and platelet activation in hypercholesterolemic rats. 2398 71