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)

A possible autocrine effect of interleukin-6 (IL-6) on the growth and differentiation of the tumor cells of 55 B-cell lymphomas was examined. Interleukin-6 was detected in a few types of B-cell lymphomas, including polymorphic immunocytoma (PI), small lymphocytic lymphoma (SLL), and immunoblastic lymphoma (IBL) with or without plasmacytoid differentiation. In PI and in IBL with plasmacytoid differentiation (IBL-P), IL-6 was detected only in immunoglobulin-containing plasmacytoid cells, and it was absent from most proliferating (Ki-67/PCNA-positive) lymphoma cells. In SLL, IL-6 was not observed in lymphoplasmacytoid cells; instead, IL-6 was observed in transformed (Ki-67/PCNA-positive) tumor cells in proliferation centers. The lymphoplasmacytoid cells in SLL exhibited a phenotype (IL-6/glutathione-S-transferase-pi [GST-pi]-negative), different from that of normal plasma cells (IL-6-negative/GST-pi-positive) and from the plasmacytoid cells (IL-6/GST-pi-positive) in PI and IBL-P. In IBL without obvious plasmacytoid differentiation, IL-6 was detected in most tumor cells that were highly proliferative (Ki-67/PCNA-positive). In this study, IL-6 was undetectable in most lymphomas related to follicular centers, in lymphoblastic lymphoma, in small noncleaved cell lymphomas of the Burkitt and non-Burkitt types, and in diffuse large cell lymphoma. This finding is compatible with a previous finding that IL-6 mRNA was absent from follicular center cells in reactive lymphoid tissues. The functions of IL-6 in these lymphomas may be quite diverse. It appears that IL-6, as an autocrine factor, is responsible for the plasmacytoid differentiation of lymphoma cells in IP and some IBL (IBL-P). The differentiation of lymphoplasmacytoid lymphoma cells in SLL, however, may not be mediated by an autocrine IL-6 mechanism. Interleukin-6 may provide a growth signal, rather than acting as a differentiation factor, for some IBL cells and for some transformed tumor cells in proliferation centers in SLL.
 ...
PMID:Functional heterogeneity and pathogenic significance of interleukin-6 in B-cell lymphomas. 141 84

Certain cytokines that are produced in liver may act as growth factors to facilitate wound healing and, hence, may influence liver regeneration. However, this hypothesis has not been directly tested. To determine whether the cytokine response evoked by partial hepatectomy (PH) modulates the process of liver regeneration, adult male rats were injected intraperitoneally with either goat polyclonal antibodies to rat tumor necrosis factor (TNF; 15 micrograms/g body wt) or an equal amount of goat anti-rat immunoglobulin G 1 h before PH. Animals were killed at 12, 24, 48, or 72 h post-PH, 1 h after injection with [3H]thymidine. Serum TNF levels were measured with the L929 cytotoxicity assay, titers of antibody to TNF were determined by enzyme-linked immunoabsorbent assay, and interleukin-6 (IL-6) concentrations were measured by B9 cell bioassay. Liver regeneration was assessed by [3H]thymidine incorporation into hepatic DNA and by immunohistochemical evidence of proliferating cell nuclear antigen (PCNA) expression. Antibodies to TNF were detected in treated rats but not in controls. Titers were highest at 12 h and progressively fell. Although TNF was never detected in serum, treatment with anti-TNF pre-PH significantly inhibited increases in serum IL-6 concentration post-PH. Anti-TNF pretreatment also inhibited [3H]thymidine incorporation into DNA, as well as expression of PCNA by both hepatocytes and liver nonparenchymal cells. These data indicate that TNF positively modulates liver regeneration after PH.
 ...
PMID:Antibodies to tumor necrosis factor-alpha inhibit liver regeneration after partial hepatectomy. 141 18

New rod photoreceptors are added to mature teleost retinas throughout life by regulated proliferation of rod precursor cells (RPCs). In this study, candidate regulators of RPC proliferation, acidic and basic fibroblast growth factors (aFGF and bFGF; 0.1 microgram/eye), interleukin-6 (IL-6; 0.1 microgram) and phytohaemagglutinin (HA15; 1.0 microgram), were injected intravitreally into one eye of goldfish (body length 5-6 cm), and mitotic RPCs in both retinas were detected and counted 3-50 days later by immunohistochemistry for proliferating cell nuclear antigen (PCNA). Retinal integrity after treatment was assessed by immunohistochemistry for tyrosine hydroxylase (TH) and other retinal antigens. All the agents applied altered the density of PCNA-immunoreactive (ir) cells in the outer and inner nuclear layers (ONL and INL) in both retinas as soon as 2-3 days after unilateral injection. Initially (2-20 days after injection), particularly in the treated retina, PCNA-ir cells appeared in clusters accompanied by various numbers of scattered individual cells, but subsequently the clusters of PCNA-ir cells disappeared while the density of singly distributed cells increased until 30 days after injection. At the doses given, these effects were most striking with aFGF and bFGF and less with IL-6 and HA15. In radial cryosections, other cellular elements immunoreactive to markers such as TH, serotonin, neuropeptide Y, substance P, glutamine synthetase, glial fibrillary acidic protein and protein kinase C, were found normal in terms of morphology. In addition, a monoclonal antibody (NN-2) was found to label some non-neuronal structures (macrophages, microglia and blood vessels) inside and outside the retina intoxicated with 6-hydroxydopamine, a few NN-2-ir cells being PCNA-positive. However, clustered PCNA-ir and marginal neuroblast cells were NN-2-negative. These results indicate that FGFs may play an important role in stimulating the proliferation of RPCs, for example, in the regeneration of fish retinas following neurotoxic destruction.
 ...
PMID:Fibroblast growth factor induces proliferating cell nuclear antigen-immunoreactive cells in goldfish retina. 751 Mar 76

The production of mature monocytes/macrophages is regulated by a group of hematopoietic growth factors, or colony-stimulating factors (CSF). We investigated the in vitro effect of human hematopoietic growth factors on human blood monocyte/macrophage differentiation and proliferation in short- and long-term in vitro cultures. The addition of macrophage CSF, granulocyte-macrophage CSF, and granulocyte CSF and interleukin-6 and interleukin-3 growth factors to monocyte/macrophage cultures induced morphological changes in cultured cells, including enhancement of cell growth and the formation of multinucleated giant cells, spindle-like cells, and fibroblast-like cells. In addition, CD4 and HLA-DR antigen expression was down regulated by the addition of growth factors without a change in the expression of other surface antigens, including CD3, CD11B, CD14, CD15, NK H1, and B1. The proliferating cell nuclear antigen was not detected in growth factor-treated nonadherent monocytes/macrophages in long-term cultures. Bromodeoxyuridine was incorporated in the adherent monocytes/macrophages, and intense staining in the small rounded cells which occur above the adherent cells in these cultures was observed after a 72-h pulse, indicating that monocytes/macrophages are slowly dividing cells.
 ...
PMID:Effect of hematopoietic growth factors on human blood monocytes/macrophages in in vitro culture. 855 11

Although previous work suggests that tumor necrosis factor-alpha (TNF) promotes liver regeneration after partial hepatectomy (PH), the source of TNF is unknown. If Kupffer cells release TNF after PH, then Kupffer cell depletion by gadolinium chloride (GdCl) should inhibit liver regeneration. To test this hypothesis, cytokine expression and regenerative events were compared in GdCl-treated and control rats. Functional assays and Northern blot analysis of a Kupffer cell-specific mRNA confirmed that GdCl depleted Kupffer cells. Despite this, semiquantitative reverse transcription-polymerase chain reaction analysis of total hepatic RNA showed six- to eightfold higher levels of TNF transcripts in GdCl-treated rats. In this group, PH caused 12-to 16-fold greater induction of interleukin-6, a TNF-inducible cytokine, and two- to threefold greater induction of several cytokine-regulated genes (c-jun, C/EBP-beta, and C/EBP-delta). GdCl also amplified regeneration-associated increases in the DNA binding activity of AP-1, a growth regulatory transcription factor. Furthermore, hepatic incorporation of [3H]thymidine, expression of the S-phase antigen, proliferating cell nuclear antigen, and the hepatocyte mitotic index were each significantly greater in GdCl-treated rats. Thus, although GdCl causes Kupffer cell depletion, it does not decrease liver TNF and actually enhances liver regeneration after PH.
 ...
PMID:Kupffer cell depletion by gadolinium chloride enhances liver regeneration after partial hepatectomy in rats. 876 96

Interleukin-6 (IL-6) has been reported to have pro- and anti-inflammatory effects. It has also been shown to cause mesangial cell proliferation in vitro and has been suggested as a mediator of injury in proliferative nephritis. We have assessed the effects of continuous infusion of human recombinant (hr) IL-6, by osmotic minipump, on the degree of glomerular injury, and on glomerular and interstitial cell proliferation, in the accelerated autologous phase of nephrotoxic nephritis. Two groups of rats were pre-immunized with 1 mg of normal rabbit IgG in Freund's complete adjuvant. One week later, nephritis was induced by an intravenous injection of 1 ml of rabbit nephrotoxic serum. One day before the induction of nephritis, group 1 (N = 9) was subcutaneously implanted with osmotic minipumps filled with 50 micrograms (200 microliters) of IL-6 (equivalent to a dose of 6 micrograms/day), while in group 2 (N = 11) the minipumps were filled with 200 microliters of normal saline. In group 3 (N = 6) normal rats were infused with 50 micrograms of IL-6 alone. The rats were killed seven days after implantation of minipumps. The administered hrIL-6 was detectable in the circulation within the pathophysiological range, and induced a hepatic acute phase response, as assessed by alpha 2-macroglobulin levels. Continuous treatment with IL-6 resulted in a significant reduction in albuminuria (from 195 +/- 37 mg/20 hr to 60 +/- 15 mg/20 hr on day 1, and from 494 +/- 52 mg/20 hr to 238 +/- 30 mg/20 hr on day 7, P < 0.002) and in the prevalence of glomerular capillary thrombosis (from 19 +/- 3% to 5 +/- 1%, P < 0.002). There was also a reduction in macrophage infiltration (ED1 + ve cells from 524 +/- 34 to 466 +/- 14 per 50 glomeruli, P < 0.02) and activation (ED3 + ve cells from 106 +/- 13 to 42 +/- 5 per 50 glomeruli, P < 0.002). Immunohistology showed fewer interstitial Ia + ve cells (OX3 and OX4) in the IL-6 treated group. Similar results were obtained in a second set of experiments in which the IL-6 treatment was extended until day 14. Kidney sections taken from nephritic rats infused with IL-6 showed no increase in glomerular or interstitial cell proliferation when stained with antibodies to proliferating cell nuclear antigen. There was no difference in the deposition of rabbit IgG or rat IgG along the glomerular basement membrane (GBM), and the titer of rat anti-rabbit IgG was similar in the IL-6 and control treated rats. Infusion of IL-6 alone in normal rats had no functional or pathological effects. In conclusion, these results show that IL-6 has powerful anti-inflammatory effects in a rat model of anti-GBM nephritis, and does not induce mesangial cell proliferation in vivo.
 ...
PMID:Abrogation of glomerular injury in nephrotoxic nephritis by continuous infusion of interleukin-6. 935 Jun 54

The relationship between the proliferating cell nuclear antigen (PCNA) expression in renal cell carcinoma (RCC) determined by immunohistochemical staining using the PC10 clone, and the preoperative serum interleukin-6 (IL-6) value determined by ELISA was examined. The secretion of IL-6 in RCC was also examined immunohistochemically using an anti-IL-6 antibody. The PCNA labeling rate was significantly higher in grade 3 tumors than in grade 1 tumors (p < 0.05), but there were no significant differences between the other grades or TNM stages. No significant correlation was obtained between the serum level of IL-6 or the positive cell rate of IL-6 and the pathological grade of the RCC. A correlation was observed between the PCNA labeling rate and positive cell rate, and between the serum IL-6 value and CRP or ESR. In conclusion, the secretion of IL-6 was detected in RCC tissue, and was suggested to be a tumor factor responsible for the growth and spread of RCC. The serum IL-6 value is considered to reflect the total secretion of IL-6 produced by the RCC and accessory cells, i.e., monocyte-macrophage lineage cells, endothelial cells and fibroblasts.
 ...
PMID:[The relationship between the production of interleukin-6 and the proliferating cell nuclear antigen (PCNA) expression in renal cell carcinoma]. 961 18

The effects of ischemia on the regenerative capacity of the liver after major tissue loss remain unclear. Interleukin-6 (IL-6) has been shown to confer protection in models of normothermic ischemia and reperfusion injury and to initiate hepatocyte proliferation after major hepatectomy. Therefore, we investigated the effects of ischemia on the regenerative capacity of the liver and evaluated the role of IL-6 in reducing reperfusion injury and enhancing hepatic proliferation in models combining ischemia and major hepatectomy. Rats subjected to 70% hepatectomy and 30 minutes of hepatic ischemia showed significantly reduced regenerative capacity (mitotic index, proliferating cell nuclear antigen, and regenerated liver weight) when compared with animals subjected to hepatectomy alone. Pretreatment of animals subjected to hepatectomy and ischemia with recombinant interleukin-6 (rIL-6) completely restored each parameter of regeneration to levels comparable with those of animals subjected to hepatectomy only. Similar results were obtained in IL-6 deficient (IL-6(-/-)) mice. IL-6(-/-) mice exposed to ischemia and hepatectomy showed impaired hepatic regeneration when compared with wild-type mice subjected to the same experimental conditions. The use of rIL-6 completely corrected each parameter of regeneration showing the specificity of IL-6 in this type of injury. The impact of IL-6 on animal survival was studied in a model combining 45 minutes of ischemia and 68% hepatectomy. Five of 7 (71%) animals pretreated with rIL-6 survived permanently, whereas all control animals died within 3 days of surgery (P =.02, Fisher's exact test). In conclusion, the study shows that ischemia dramatically impairs the regenerative capacity of the liver. IL-6 appears to be a key protective molecule in reducing injury and promoting regeneration following combined ischemia and major tissue loss.
 ...
PMID:Ischemia impairs liver regeneration after major tissue loss in rodents: protective effects of interleukin-6. 1042 56

The mediators of cutaneous metallothionein induction by ultraviolet radiation have not been defined. In this study we sought to identify cytokines that might be involved. We examined the role of interleukin-6, using the IL-6 null (IL-6-/-) mouse, which has been observed to be highly sensitive to ultraviolet radiation damage. Whereas cutaneous metallothionein concentration, measured by radioimmunoassay, began to rise in wild-type (IL-6+/+) mice by 12 h after ultraviolet irradiation, there was a significant delay in the IL-6-/- mice until 48 h after UV irradiation. Immunohistologically, metallothionein appeared in IL-6+/+ mice at 24 h in dermal fibroblasts, and then by 48 h in epidermal basal keratinocytes, with intensity increasing until 72 h, and was coincident with proliferating cell nuclear antigen-positive staining. Corresponding metallothionein expression in IL-6-/- mouse skin was significantly delayed. Serum interleukin-6 was elevated in IL-6+/+ mice following ultraviolet irradiation, with peak concentration at 4 h, but no increase in serum interleukin-1beta was found in either IL-6+/+ or IL-6-/- mice. Interestingly, tumor necrosis factor alpha concentration in serum was elevated at 12 h postirradiation in IL-6+/+ mice, but there was an earlier (at 4 and 8 h) time-dependent increase in tumor necrosis factor alpha in serum of the IL-6-/- mice. Skin zinc and copper concentrations were not altered by ultraviolet irradiation in either IL-6+/+ or IL-6-/- mice. The results suggest that interleukin-6 may be a very early mediator of cutaneous metallothionein induction by ultraviolet radiation, but that this role is possibly assumed by alternative cytokines like tumor necrosis factor alpha when interleukin-6 is deficient.
 ...
PMID:Cutaneous metallothionein induction by ultraviolet B irradiation in interleukin-6 null mice. 1065 96

Proliferating astrocytes are frequently observed in diseased and injured brains. These newly generated astrocytes are necessary to reestablish the barriers that isolate the CNS from the rest of the body; however, they also create a matrix that inhibits regeneration and remyelination. Therefore, it is important to understand the mechanisms that enable a terminally differentiated astrocyte to reenter the cell cycle. Ciliary neurotrophic factor (CNTF), interleukin-6 (IL-6), transforming growth factor-alpha (TGF-alpha), and fibroblastic growth factor-2 (FGF-2) are four cytokines that are rapidly elevated in damaged neural tissue. These cytokines also have been implicated in glial scar formation. We sought to determine whether IL-6 and CNTF stimulate astroglial proliferation alone or in combination with other mitogens. Intraparenchymal CNTF modestly increased the number of proliferating cell nuclear antigen (PCNA) and glial fibrillary acidic protein (GFAP) double positive astrocytes when introduced by stereotactic injection into the adult rat brain. When applied directly to highly enriched rat forebrain astrocyte cultures, neither CNTF nor IL-6-stimulated DNA synthesis. Therefore, they are not astroglial mitogens. However, both cytokines synergized with epidermal growth factor (EGF), increasing its mitogenicity by approximately twofold. Astrocytes that had been "aged" for at least 3 weeks in vitro became refractory to EGF; however, when these "aged" astrocytes were pretreated with either IL-6 or CNTF for as little as 2 h, they became competent to reenter the cell cycle upon exposure to EGF. These data suggest that IL-6 type cytokines, likely by activating STAT family transcription factors, induce the expression of signaling molecules that endow resting astrocytes with the competence to respond to mitogens and to reenter the cell cycle.
 ...
PMID:IL-6-type cytokines enhance epidermal growth factor-stimulated astrocyte proliferation. 1110 72


1 2 3 4 5 6 7 Next >>