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)

Evidence has accumulated in the last few years that the expression of the microsomal/peroxidase antigen (M/TPO-Ag) in thyroid cells is induced by TSH, through pathways which involve intracellular cAMP accumulation and protein synthesis. These data have been found true in any thyroid system studied so far, both in terms of immunologic and enzymatic activity of TPO. TSH and cAMP also increase the levels of the specific mRNA for TPO in thyroid cells from different species. Whether this phenomenon is due to a direct transcriptional regulation of the TPO gene, as shown in dog thyroid cells, or to posttranscriptional effects, as it would appear in FRTL-5 cells, remains to be clarified by future experiments. Thyroid stimulating antibody (TSAb) of Graves' disease also stimulates the expression of M/TPO-Ag. This finding gives further support to the relevance of TSAb in the pathogenesis of hyperthyroidism and explains the well known observation that the "microsomal" antigen is particularly abundant in glands of Graves' patients. The modulation of M/TPO-Ag surface expression by TSH can explain the decrease of circulating anti-MAb observed during L-thyroxine therapy in hypothyroid patients with Hashimoto's thyroiditis. Other agents, such as methimazole and sodium iodide, which influence thyroid cell function, do not directly interfere with the expression of M/TPO-Ag. Cytokines, such as gamma-interferon, interleukin-1, and interleukin-6 have been shown to inhibit the TSH-induced increase of TPO mRNA, but further investigations are required to elucidate the exact role of cytokines in the regulation of M/TPO-Ag expression.
 ...
PMID:The microsomal/peroxidase antigen: modulation of its expression in thyroid cells. 166 95

Serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), soluble P-selectin, and soluble L-selectin (sL-selectin), tumor necrosis factor-alpha, and interleukin-6 were measured in patients with Graves' disease (GD) (n = 33), in patients with toxic nodular goiter (n = 34), and in a group of healthy controls (n = 36). The serum levels of sICAM-1, sVCAM-1, sE-selectin, and sL-selectin were markedly elevated in patients with GD and in patients with toxic nodular goiter before treatment with methimazole (P < 0.05 for all). After 8 weeks of therapy, serum concentrations of sVCAM-1 and sE-selectin normalized, whereas serum levels of sL-selectin and sICAM-1 remained elevated. Hormone concentrations normalized after 2 weeks, clearly preceding falling levels of circulating adhesion molecules. Serum concentrations of soluble P-selectin, TNF-alpha, and interleukin-6 did not differ among patients with GD and toxic nodular goiter and healthy subjects. Serum levels of sVCAM-1 and sICAM-1 correlated with the serum concentrations of TSH receptor antibodies (n = 33; r = 0.921 and r = 0.792, respectively) and thyroid peroxidase antibodies (n = 33; r = 0.682 and r = 0.761, respectively) but not thyroglobulin antibodies. However, no correlation between serum levels of sE-selectin, sL-selectin, and soluble P-selectin or cytokines and serum levels of thyroid peroxidase antibodies, TSH receptor antibodies, or thyroglobulin antibodies, respectively, was found. In addition, no correlation between serum levels of adhesion molecules or cytokines and thyroid hormones was seen. We conclude that both the action of thyroid hormones and the autoimmune process in GD may contribute to elevated levels of soluble adhesion molecules.
 ...
PMID:Circulating selectins, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in hyperthyroidism. 754 2

We have further characterized the biological activities, mechanism of action, and target cell populations of recombinant human and murine thrombopoietin (rhTPO and rmTPO) in in vitro human and murine model systems. Alone, hTPO or mTPO stimulated the maturation of immature murine megakaryoblasts as measured in a single cell assay. The combination of hTPO or mTPO and interleukin-6 (IL-6) resulted in a further increase in megakaryocyte differentiation in this system. Murine TPO stimulated mouse megakaryocyte progenitor development. Human megakaryocyte progenitor development was potentiated by hTPO alone and further augmented in the presence of the early-acting cytokines (IL-3) or kit ligand/stem cell factor (KL/SCF). To further define the mechanism of action of TPO, neutralization studies were performed with antisera to IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-1 beta, and IL-11. No diminution in TPO activity was observed in the presence of these antisera. Moreover, because adhesive interactions are known to modulate hematopoiesis, we studied whether hTPO might alter such interactions between human bone marrow (BM) megakaryocytes and human BM stromal fibroblasts. No changes were observed in either megakaryocyte expression of the surface molecules lymphocyte function-associated antigen-1, very late activation antigen-4, or intercellular adhesion molecule-1 or the adhesion of megakaryocytes to stromal fibroblasts after treatment with the growth factor. Furthermore, no induction of secretion of the cytokines IL-1 alpha, IL-1 beta, GM-CSF, IL-6, granulocyte-CSF, tumor necrosis factor-alpha, transforming growth factor-beta 1, or transforming growth factor-beta 2 by primary human BM megakaryocytes was noted after treatment of the cells with hTPO. To address whether TPO affects very primitive hematopoietic progenitors, we studied the residual cells from the BMs of mice treated with high doses of 5-fluorouracil. Although no effect of mTPO alone was noted on the viability or replication of such primitive murine progenitor populations, the triple combination of IL-3 + KL/SCF + TPO stimulated growth of megakaryocyte progenitors. These results indicate that TPO is a highly lineage-specific growth factor whose primary biological effects are likely to be direct modulation of the growth and maturation of committed megakaryocyte precursors and immature megakaryoblasts.
 ...
PMID:Modulation of megakaryocytopoiesis by thrombopoietin: the c-Mpl ligand. 763 39

Previous reports have shown that interleukin-6 (IL-6) enhances the responsiveness of platelets to thrombin stimulation and has modest thrombocytopoietic effects in vivo. Thrombopoietin (TPO; mpl ligand) has been shown to have dramatic thrombocytopoietic effect in vivo, but little is known of its capacity to alter platelet function. In this study, a direct comparison of the effects of IL-6 and TPO on platelet function in dogs has been performed, with modest doses of TPO (1 microgram/kg/d) chosen to match or moderately exceed the platelet counts achieved with IL-6 (40 micrograms/kg/d) for 10 days. Platelet responsiveness to thrombin stimulation was assessed in TPO-treated, IL-6-treated, and control dogs by flow cytometric measurement of P-selectin expression. On day 5, the dose of thrombin promoting half maximal stimulation (EC50) of platelets was not significantly changed in TPO-treated dogs, whereas in IL-6-treated dogs the EC50 decreased to 73.1% +/- 6.1% (mean +/- 1 SD; n = 5) of control values (P < 0.01). These experiments were performed on both gel-filtered platelets and washed whole blood, indicating that the observed changes in EC50 were caused by cytokine-mediated alteration of platelets rather than plasma components. Because it has been shown that thiazole orange specifically labels a subpopulation of dog platelets that is less than 24 hours old, the thrombin responsiveness of these young, newly synthesized platelets was determined. The EC50 of thiazole orange-positive platelets from IL-6-treated dogs decreased dramatically by day 5 to 46.5% +/- 13.1% (n = 4) of control values (P < 0.001), whereas TPO-treated dogs did not significantly change. When TPO was directly incubated with platelets ex vivo, no effects on either thrombin-mediated P-selectin expression or adenosine diphosphate-induced fibrinogen binding were observed. These data show that IL-6 alters platelet function, as measured by reactivity to thrombin, whereas TPO does not. This divergence in function is observed even though TPO is equally, or more, effective at promoting platelet production under these experimental conditions.
 ...
PMID:Relative reactivity of platelets from thrombopoietin- and interleukin-6-treated dogs. 863 74

We studied a wide variety of surgical patients to determine whether serum levels of interleukin-6 (IL-6) or tumor necrosis factor-alpha (TNF-alpha) correlate with the changes in serum thyroid hormone levels of the postoperative period. Surgical procedures were divided into minor surgery (cholecystectomy, n = 12), moderate surgery (colorectal cancer and stomach cancer, n = 54), and extensive surgery (esophageal cancer or pancreatic cancer, n = 6). One day after surgery, serum free T3 levels decreased in all 3 groups when compared to the preoperative values; serum free T4 levels did not change regardless of surgical procedure. Serum TSH levels decreased significantly 1 day after surgery in the groups of moderate and extensive surgery. Serum levels of IL-6 increased 12 h after surgery and began to decrease gradually thereafter. There was no change in serum levels of TNF-alpha before and after surgery. The increment of serum IL-6 was dependent on the surgical procedures: the more extensive the surgery, the greater the increase in serum IL-6. Serum free T3 and free T4 levels were inversely correlated with the serum levels of IL-6. To further examine whether IL-6 is responsible for alteration of thyroid hormone production, cultured porcine thyroid follicles were exposed to 0 to 20 ng/ml of recombinant human IL-6 for 24 to 48 h. Then, type 1 5'-deiodinase activity (T4 to T3 converting enzyme), iodide uptake, and thyroid peroxidase (TPO) activity were measured. Our in vitro experiments showed no effect of IL-6 on these parameters. In summary, surgical procedure can cause elevation of serum IL-6 and decrease in serum free T3 levels. However, IL-6 alone does not appear to be a strong candidate for alteration of thyroid hormone production including T3 generation from T4.
 ...
PMID:Elevated serum interleukin-6 and decreased thyroid hormone levels in postoperative patients and effects of IL-6 on thyroid cell function in vitro. 900 Nov 95

Formation of proplatelets from megakaryocytes is believed to be the first step of platelet production in vitro. In this study, we evaluated the effects of recombinant human thrombopoietin (hTPO) on the development of proplatelets from a GpIIb/IIIa+ population of rat bone marrow cells highly enriched for late megakaryocyte progenitors (GpIIb/IIIa+ CFU-MK) that we recently found to be a primary target population of TPO. Quantitative measurement of hTPO-induced proplatelet formation was performed in liquid cultures. Proplatelet formation from megakaryocytes derived from GpIIb/IIIa+ CFU-MK in the presence of hTPO began on day 4 of culture and peaked the following day. On day 5 of culture, lower concentrations of hTPO expanded the number of megakaryocytes, increased the number of proplatelets and the percentage of proplatelet-developing megakaryocytes. Increasing hTPO concentrations resulted in a modest decrease in proplatelet development. We next used hTPO to derive immature or mature megakaryocytes from GpIIb/IIIa+ CFU-MK. These populations of cultured megakaryocytes spontaneously formed proplatelets when recultured in the absence of exogenous hTPO. The addition of hTPO at higher concentrations modestly augmented proplatelet production from immature megakaryocytes derived from 2-day liquid cultures. However, either murine interleukin-6 (IL-6) or human IL-11, but not rat IL-3, was more potent than hTPO in augmenting proplatelet formation from immature megakaryocytes. Each of these four cytokines had an inhibitory effect on proplatelet formation from more differentiated megakaryocytes derived from 3-day liquid cultures. These results indicate that TPO enhances proplatelet production primarily by stimulating CFU-MK to increase the number of proplatelet-forming megakaryocytes and that its action is clearly different from those of other cytokines that also stimulate megakaryocytopoiesis.
 ...
PMID:Action of thrombopoietin at the megakaryocyte progenitor level is critical for the subsequent proplatelet production. 901 17

The recombinant hemopoietic factors of megakaryocyte potentiator (MEG-POT) were studied to compare their activity in stimulating proplatelet process formation (PPF) with thrombopoietin (TPO, c-MpI ligand). For the assay, a highly enriched (> 95%) population of more than 90% viable megakaryocytes was isolated from rat bone marrow using the immunomagnetic beads method and cultured with fetal calf serum (FCS) or in a serum-free condition. Megakaryocytes developing slender beaded cytoplasmic processes (proplatelet processes) were observed on both inverted phase contract microscopy and scanning electron microscopy. A large number of proplatelet process clusters were dose-dependently formed with the addition of varying doses of recombinant erythropoietin (rEpo) and interleukin-6 (rIL-6) as well as TPO. Epo and IL-6 were demonstrated to act synergistically solely at low doses in the development of PPF (P < 0.05). Other recombinant factors such as IL-11, leukemia inhibitory factor (LIF) and erythroid differentiation factor (EDF) appeared weak or ineffective. From these in vitro observations, it was suggested that a synergism of Epo and IL-6 might play a significant role in the terminal stage of megakaryocyte maturation leading to platelet release.
 ...
PMID:Synergistic effects of erythropoietin and interleukin-6 on the in vitro proplatelet process formation of rat megakaryocytes. 911 Mar 49

In order to examine which cytokine could be used as a marker of the biological effect of thyroid hormones or anti-thyroid antibodies in Graves' disease (GD) patients, we simultaneously evaluated the concentrations of TSH, free thyroid hormones (fT3 and fT4), anti-thyroid antibodies (anti-TPO and anti-TG) and a group of cytokines: interleukin-2 (IL-2), tumour necrosis factor alpha (TNFalpha), interleukin-6 (IL-6) and their soluble receptors (sIL-2R, sTNFalphaR, sIL-6R) as well as interleukin-10 (IL-10) in eight GD females and nine normal controls. We found that serum sIL-2R concentrations of GD patients had only the tendency to be higher versus controls, but strong positive correlations between fT3 and fT4 and sIL-2R in peripheral blood of GD subjects were revealed. We showed that sIL-2R was the best cytokine marker, showing very good correlation with the endocrine status of GD patients.
 ...
PMID:Cytokines serum levels as the markers of thyroid activation in Graves' disease. 955 56

Postpartum thyroid dysfunction (PPTD) is an autoimmune-mediated thyroid destructive process. Human interleukin-6 (IL-6) is a cytokine found to be increased in subacute thyroiditis, amiodarone-induced thyrotoxicosis, Graves' disease, and other thyroid destructive processes. We report serum IL-6 levels in PPTD in two independent studies. New York Study: In a previous prospective study we demonstrated that PPTD occurred in 25% (7/28) of women with type 1 diabetes mellitus. IL-6 determinations were made on the frozen serum samples of these 28 women during each trimester of their pregnancy and at 1.5, 3, 6, 9, and 12 months postpartum. IL-6 levels were found to be similar in women with PPTD compared with women without PPTD (mean 3.06+/-2.25 vs. 2.51+/-2.21 pg/mL; p = 0.15). No difference in IL-6 levels was found between the pre- and the postpartum periods (mean 2.67+/-1.82 vs. 3.04+/-2.44 pg/mL; p = 0.30) in all 28 women. Cardiff Study: Serum IL-6 levels were measured on frozen serum samples of 30 women with PPTD. IL-6 levels were below the detection limit (25 fmol/L or 0.65 pg/mL) in 94 (67%) of these samples. No significant difference in the mean serum IL-6 levels were found between any time points in the study. There was no correlation between serum IL-6 levels, thyroid peroxidase (TPO)- antibodies and serum thyrotropin (TSH) levels at any time point. IL-6 levels during pregnancy or postpartum were not found to be significantly different in women with PPTD compared with women without PPTD.
 ...
PMID:Interleukin-6 levels are not increased in women with postpartum thyroid dysfunction. 962 26

The effects of thrombopoietin (TPO; c-mpl ligand), FLT3/FLK-2 ligand (FL), and interleukin-6 (IL-6) on the survival of murine hematopoietic long-term reconstituting cells (LTRC) were studied by using lineage-negative, Sca-1-positive, c-kit-positive (Lin-Sca-1(+)c-kit+) marrow cells from 5-fluorouracil-treated mice. We tested the ability of these cytokines to maintain the viability of LTRC by transplanting the cultured cells to lethally irradiated Ly-5 congenic mice together with compromised marrow cells. As a single agent, only TPO could maintain the LTRC. Neither IL-6 nor FL was effective by itself, but they acted synergistically to maintain the LTRC. We examined whether the maintenance of LTRC by these cytokines was due to the survival of stem cells or was the result of active cell divisions and self-renewal. To monitor cell division, we used membrane dye PKH26. Enriched cells were stained with PKH26 on day 0 and incubated in suspension culture with TPO or with IL-6 and FL for 7 days. On day 7, PKH26(low) and PKH26(high) cells were prepared by sorting and their in vivo reconstituting abilities were tested by transplantation into lethally irradiated Ly-5 congenic mice together with compromised marrow cells. PKH26(high) populations cultured with both TPO alone and the combination of IL-6 and FL showed greater reconstitution activity than that of PKH26(low) populations. These data indicate that TPO alone and the combination of IL-6 and FL can support the survival of stem cells without stimulating their active cell proliferation.
 ...
PMID:Thrombopoietin promotes the survival of murine hematopoietic long-term reconstituting cells: comparison with the effects of FLT3/FLK-2 ligand and interleukin-6. 965 44


1 2 Next >>