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

In vitro culture of rodent microglia is a common system used to model proinflammatory changes in the brain. However, typical postnatal brain isolation protocols are time consuming and cell numbers acquired are often a rate-limiting factor for experimental progress. Large studies that rely on the use of primary microglia can, therefore, require excessive numbers of animals at considerable expense, additional technical support and culture incubator space. Although the addition of mitogens such as macrophage colony-stimulating factor, granulocyte macrophage-colony stimulating factor, and epidermal growth factor to the cultures can facilitate a higher yield, this adds additional expense and likely alters the microglial phenotype. We have defined a simple, inexpensive modification of our standard culture protocol that allows us to repetitively isolate microglia. In order to define a method for improving microglia yield, we utilized our standard mixed glial culture preparation derived from postnatal day 1-3 mouse brains. After isolating microglia from mixed cultures at 14 days in vitro, we added fresh media to the cultures for an additional 7 and 14 days to monitor microglial proliferation. We acquired a constant number of cells at each successive time point although the numbers were reduced from the first isolation. More importantly, in order to determine if our successive microglia isolates differed phenotypically we characterized several parameters of function. We compared their ability to secrete the proinflammatory cytokines interleukin-6 and tumor necrosis factor alpha after LPS stimulation. We also contrasted the phagocytic ability, morphology, and specific immunoreactivity (CD11b, CD68, CD45 and MHC II) of the culture ages. Our data demonstrate that microglia can be obtained from extended-time cultures provided periodic isolation is performed. Moreover, the cells retain a comparable in vitro phenotype. This demonstrates that cells from all ages can be combined for any given study. These findings are a viable and inexpensive way to increase and extend the microglial yield without increasing the number of animals used or adding costly mitogens. This method will be particularly useful for the preparation of microglia cultures from limited transgenic colonies.
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PMID:Microglia repetitively isolated from in vitro mixed glial cultures retain their initial phenotype. 1755 68

Immunophenotype of mobilized stem blood cells (CD34+) was studied in 29 patients with late post-traumatic spinal lesions. The CD34+ cells demonstrated different levels of expression of CD45, CD38, monomorphic determinants HLA-DR and gp130 epitopes. Most patients presented with a CD34+ cell fraction with no or low expression of common leukocytic antigen CD45. Only 2 patients had greater than 15 percent of HLA-DR-CD38- cells in the CD34+ fraction. A common transducer molecule of interleukin-6 family cytokines gp130 was expressed on stem (CD34+) cells in all the cases, 26 percent of the patients had an activated gp130 phenotype, i.e. a combination of C7+ and A1- epitopes.
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PMID:Immunophenotypic peculiarities of mobilized stem (CD34+) cells in blood from patients with severe spinal cord injury. 1808 53

A plethora of myeloma growth factors (MGFs) has been identified, but their relative importance and cooperation have not been determined. We investigated 5 MGFs (interleukin-6 [IL-6], insulin-like growth factor type 1 [IGF-1], hepatocyte growth factor [HGF], HB-epidermal growth factor [HB-EGF], and a proliferation-inducing ligand [APRIL]) in serum-free cultures of human myeloma cell lines (HMCLs). In CD45(-) HMCLs, an autocrine IGF-1 loop promoted autonomous survival whereas CD45(+) HMCLs could not survive without addition of MGFs, mainly IGF-1 and IL-6. IGF-1 was the major one: its activity was abrogated by an IGF-1R inhibitor only, whereas IL-6, HGF, or HB-EGF activity was inhibited by both IGF-1R- and receptor-specific inhibition. APRIL activity was inhibited by its specific inhibitor only. Of the investigated MGFs and their receptors, only expressions of IGF-1R and IL-6R in multiple myeloma cells (MMCs) of patients delineate a group with adverse prognosis. This is mainly explained by a strong association of IGF-1R and IL-6R expression and t(4;14) translocation, but IGF-1R expression without t(4;14) can also have a poor prognosis. Thus, IGF-1-targeted therapy, eventually in combination with anti-IL-6 therapy, could be promising in a subset of patients with MMCs expressing IGF-1R.
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PMID:The role of IGF-1 as a major growth factor for myeloma cell lines and the prognostic relevance of the expression of its receptor. 1922 10

Galectin-1 is a galactoside-binding lectin expressed in multiple tissues that has pleiotropic immunomodulatory functions. We previously showed that galectin-1 activates human monocyte-derived dendritic cells (MDDCs) and triggers a specific genetic program that up-regulates DC migration through the extracellular matrix, an integral property of mucosal DCs. Here, we identify the galectin-1 receptors on MDDCs and immediate downstream effectors of galectin-1-induced MDDC activation and migration. Galectin-1 binding to surface CD43 and CD45 on MDDCs induced an unusual unipolar co-clustering of these receptors and activates a dose-dependent calcium flux that is abrogated by lactose. Using a kinome screen and a systems biology approach, we identified Syk and protein kinase C tyrosine kinases as mediators of the DC activation effects of galectin-1. Galectin-1, but not lipopolysaccharide, stimulated Syk phosphorylation and recruitment of phosphorylated Syk to the CD43 and CD45 co-cluster on MDDCs. Inhibitors of Syk and protein kinase C signaling abrogated galectin-1-induced DC activation as monitored by interleukin-6 production; and MMP-1, -10, and -12 gene up-regulation; and enhanced migration through the extracellular matrix. The latter two are specific features of galectin-1-activated DCs. Interestingly, we also found that galectin-1 can prime DCs to respond more quickly to low dose lipopolysaccharide stimulation. Finally, we underscore the biological relevance of galectin-1-enhanced DC migration by showing that intradermal injection of galectin-1 in MRL-fas mice, which have a defect in skin DC emigration, increased the in vivo migration of dermal DCs to draining lymph nodes.
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PMID:Galectin-1 co-clusters CD43/CD45 on dendritic cells and induces cell activation and migration through Syk and protein kinase C signaling. 1963 95

Two distinct bone marrow-derived blast colony-forming cells can generate colonies of lineage-restricted progenitor cells in agar cultures of murine bone marrow. Both cell types selectively had a Kit(+) ScaI(+) phenotype distinguishing them from most lineage-restricted progenitor cells. Multicentric blast colony-forming cells stimulated by stem cell factor plus interleukin-6 (IL-6) (BL-CFC-S) were separable from most dispersed blast colony-forming cells stimulated by Flt3 ligand and IL-6 (BL-CFC-F) using CD34 and Flt3R probes. Multicentric BL-CFC-S cofractionated with colony-forming units, spleen (CFU-S) supporting the possibility that the 2 cells may be identical. The colony populations generated by BL-CFC-S were similar in their phenotype and proliferative capacity to progenitor cells in whole bone marrow but the progeny of BL-CFC-F were skewed with an abnormally high proportion of Kit(-) Flt3R(+) cells whose clonogenic cells tended to generate only macrophage progeny. Both blast colony populations had a high percentage of GR1(+) and Mac1(+) cells but BL-CFC-F colonies also contained a significant population of B220(+) and IL-7R(+) cells relevant to the superior ability of BL-CFC-F colony cells to generate B lymphocytes and the known dependency of this process on Flt3 ligand and IL-7. The commitment events and phenotypic changes during the generation of differing progenitor cells in blast colonies can now be clonally analyzed in a convenient in vitro culture system.
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PMID:Murine hematopoietic blast colony-forming cells and their progeny have distinctive membrane marker profiles. 1985 4

Hearing impairment can be the cause of serious socio-economic disadvantages. Recent studies have shown inflammatory responses in the inner ear co-occur with various damaging conditions including noise-induced hearing loss. We reported pro-inflammatory cytokine interleukin-6 (IL-6) was induced in the cochlea 6h after noise exposure, but the pathophysiological implications of this are still obscure. To address this issue, we investigated the effects of IL-6 inhibition using the anti-IL-6 receptor antibody (MR16-1). Noise-exposed mice were treated with MR16-1 and evaluated. Improved hearing at 4kHz as measured by auditory brainstem response (ABR) was noted in noise-exposed mice treated with MR16-1. Histological analysis revealed the decrease in spiral ganglion neurons was ameliorated in the MR16-1-treated group, while no significant change was observed in the organ of Corti. Immunohistochemistry for Iba1 and CD45 demonstrated a remarkable reduction of activated cochlear macrophages in spiral ganglions compared to the control group when treated with MR16-1. Thus, MR16-1 had protective effects both functionally and pathologically for the noise-damaged cochlea primarily due to suppression of neuronal loss and presumably through alleviation of inflammatory responses. Anti-inflammatory cytokine therapy including IL-6 blockade would be a feasible novel therapeutic strategy for acute sensory neural hearing loss.
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PMID:Blockade of interleukin-6 signaling suppressed cochlear inflammatory response and improved hearing impairment in noise-damaged mice cochlea. 2002 35

Our aim was to analyze the effects of dexamethasone (Dx) (1mg/kg), prophylactically or therapeutically administered, on the inflammatory response triggered by peripheral blood leukocytes during acute pancreatitis (AP) induced in rats by bile-pancreatic duct obstruction (BPDO) and their consequences in the progress of the disease. Flow cytometry was used to analyze the distribution of the major leukocyte populations, the CD45 expression and the activated state of monocytes as reflected by the membrane-bound intercellular adhesion molecule-1 (ICAM-1) and the production of tumor necrosis factor-alpha (TNF-alpha) and monocyte chemoattract protein-1 (MCP-1) in response to lipopolysaccaride (LPS). Interleukin-6 (IL-6) plasma levels, pancreatic fluid content and histology of pancreas sections were also evaluated. Dx, given either before or after AP, blunted the monocyte increase induced by BPDO-induced AP, but did not change lymphocyte and neutrophil counts. Membrane-bound ICAM-1 expression did not vary in circulating monocytes during BPDO, either in Dx-treated or non-treated rats. Both Dx treatments inhibited TNF-alpha and MCP-1 production in non-stimulated and LPS-stimulated monocytes, whose response was found to be higher than in controls from early AP. Leukocyte CD45 expression was found to be reduced in rats with AP and shifted to control values in Dx-post-treated rats. Cytokinemia as well as pancreatic edema and leukocyte infiltration found in BPDO rats were reduced by Dx given either before or after AP. We conclude that prophylactic and therapeutic Dx treatments inhibited the inflammatory response triggered by circulating leukocytes in rats with BPDO-induced AP, thus contributing to reducing the severity of the disease.
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PMID:Effect of dexamethasone on peripheral blood leukocyte immune response in bile-pancreatic duct obstruction-induced acute pancreatitis. 2015 47

We have shown previously that rotavirus (RV) can infect murine intestinal B220(+) cells in vivo (M. Fenaux, M. A. Cuadras, N. Feng, M. Jaimes, and H. B. Greenberg, J. Virol. 80:5219-5232, 2006) and human blood B cells in vitro (M. C. Mesa, L. S. Rodriguez, M. A. Franco, and J. Angel, Virology 366:174-184, 2007). However, the effect of RV on B cells, especially those present in the human intestine, the primary site of RV infection, is unknown. Here, we compared the effects of the in vitro RV infection of human circulating (CBC) and intestinal B cells (IBC). RV infected four times more IBC than CBC, and in both types of B cells the viral replication was highly restricted to the memory subset. RV induced cell death in 30 and 3% of infected CBC and IBC, respectively. Moreover, RV induced activation and differentiation into antibody-secreting cells (ASC) of CBC but not IBC when the B cells were present with other mononuclear cells. However, RV did not induce these effects in purified CBC or IBC, suggesting the participation of other cells in activating and differentiating CBC. RV infection was associated with enhanced interleukin-6 (IL-6) production by CBC independent of viral replication. The infection of the anti-B-cell receptor, lipopolysaccharide, or CpG-stimulated CBC reduced the secretion of IL-6 and IL-8 and decreased the number of ASC. These inhibitory effects were associated with an increase in viral replication and cell death and were observed in polyclonally stimulated CBC but not in IBC. Thus, RV differentially interacts with primary human B cells depending on their tissue of origin and differentiation stage, and it affects their capacity to modulate the local and systemic immune responses.
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PMID:Rotavirus differentially infects and polyclonally stimulates human B cells depending on their differentiation state and tissue of origin. 2016 28

Src homology 2 domain-containing inositol 5-phosphatase (SHIP(-/-)) animals display an age-related increase in interleukin-6 (IL-6), a decrease in B lymphopoiesis, and an elevation in myelopoiesis. We investigated the origin of the IL-6 production and show that it is largely produced by peritoneal and splenic macrophages. IL-6 production by these macrophages is not a direct result of the loss of SHIP: IL-6 production is not spontaneous, is absent from bone marrow-derived macrophages, declines with prolonged culture of macrophages, and requires a stimulus present in vivo. The IL-6-rich peritoneal cavity of SHIP(-/-) mice shows more than 700-fold more immunoglobulin G (IgG) than wild-type, approximately 20% of which is aggregated or in an immune complex and contains B220(+) cells that secrete IgG. The SHIP-deficient peritoneal macrophages show evidence of IgG receptor stimulation. Animals lacking both the signal-transducing gamma-chain of IgG receptors and SHIP or Ig and SHIP produce less IL-6. The data indicate a feed-forward process in which peripheral macrophages, responding through IgG receptors to secreted IgG, produce IL-6, to support further B-cell production of IgG. Because of the proinflammatory phenotype of SHIP(-/-) animals, these findings emphasize the importance of IL-6-neutralizing strategies in autoimmune and proinflammatory diseases.
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PMID:IL-6 increases B-cell IgG production in a feed-forward proinflammatory mechanism to skew hematopoiesis and elevate myeloid production. 2035 5

A flow cytometric method for the identification of chicken blood leukocyte subpopulations and thrombocytes was developed. An anti-chicken CD45 phycoerythrin-labelled antibody was used to separate leukocytes from red blood cell nuclei. Leukocytes and thrombocytes were identified using a combination of their CD45-positivity and their typical side scatter properties. The identity of the CD45-positive cells was confirmed by sorting the subpopulations and subsequent light microscopic evaluation. In these differentiated cell populations, intracellular expression analysis of the proinflammatory cytokines interleukin-1beta and interleukin-6 was subsequently optimized on whole blood after in vitro stimulation with lipopolysaccharide from Escherichia coli strain O127:B8.
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PMID:Flow cytometric differentiation of avian leukocytes and analysis of their intracellular cytokine expression. 2039 May 35


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