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)

Recent investigations of immunologic events in systemic sclerosis focus on the identification of which immune system cells are participating in the disease process, what antigens are stimulating the T and B cells, which cytokines are involved, and which cell adhesion molecules promote cell-cell and cell-extracellular matrix interactions. Increased numbers of gamma/delta and activated CD4+ T cells are present in involved skin of line-200 chickens, an animal model of systemic sclerosis. CD4+ T cells from patients with systemic sclerosis are stimulated by human type I collagen, and immunoglobulins from some patients with systemic sclerosis bind retroviral proteins, the terminal galactosyl (alpha 1-3)-galactose disaccharide of laminin, or a 138 amino acid region of the PM-Scl antigen. The development of an anticentromere antibody response in patients with systemic sclerosis appears to require the presence of a polar amino acid at position 26 in the antigen-binding cleft of the HLA-DQB1 molecule. Interleukin-2, interleukin-4, interleukin-6, and transforming growth factor-beta have been implicated as cytokines that may be involved in the pathogenesis of systemic sclerosis. Increased expression of intercellular adhesion molecule 1 (ICAM-1) on systemic sclerosis fibroblasts is responsible for increased binding of T cells to those fibroblasts through ICAM-1/lymphocyte function-associated antigen 1 interactions. beta 1 and beta 2 integrins, ICAM-1, and endothelial leukocyte adhesion molecule 1 all may be involved in the homing of lymphocytes to involved skin in patients with systemic sclerosis.
Curr Opin Rheumatol 1992 Dec
PMID:Immunologic aspects of scleroderma. 145 82

Scleroderma fibrotic lesions demonstrate vascular disease, mononuclear cell infiltrates, and increased collagen. Fibroblasts in these lesions are activated to synthesize increased extracellular matrix substances, a phenotype that continues when these cells are removed and grown in tissue culture. Levels of messenger RNA for connective-tissue substances, measured directly in biopsies of scleroderma skin, show increased message for type I collagen, but not type III collagen or fibronectin. Increased procollagen type I in scleroderma skin occurs in the papillary dermis, perivascular areas, and deep interstitium, even in skin areas that are not yet fibrotic. Scleroderma fibroblasts express more intercellular adhesion molecule 1 on their surfaces than do normal cells, and this molecule is increased in endothelial cells, mononuclear cells, and fibroblasts. In vitro scleroderma fibroblasts adhere more frequently to extracellular matrix substances and retract collagen lattices to a greater extent. Peripheral blood lymphocytes from scleroderma patients produce excessive amounts of interleukin-2 when incubated with type I collagen, and circulating basophils release more histamine than do normal cells. There is evidence for activated eosinophils both in the dermis and pulmonary lesions in scleroderma, which may play a role in fibrosis. Transforming growth factor-beta is overexpressed by alveolar macrophages from patients with fibrotic pulmonary disease. Scleroderma fibroblasts, when exposed to transforming growth factor-beta, overexpress the alpha-type receptor for platelet-derived growth factor. Scleroderma sera more frequently contain measurable quantities of interleukin-4, interleukin-6, and interleukin-2. Interleukin-4 causes adult dermal fibroblasts to proliferate and to make interleukin-6. Interleukin-6 has been shown to stimulate fibroblast synthesis of collagen and glycosaminoglycans.(ABSTRACT TRUNCATED AT 250 WORDS)
Curr Opin Rheumatol 1992 Dec
PMID:Connective tissue metabolism including cytokines in scleroderma. 145 83

Similarities between the N-terminal regions of the three subunits of the clotting protein fibrinogen--(alpha beta gamma)2--suggest that they evolved from a common progenitor. However, to date no human alpha chain has been found with the strong C-terminal homology shared by the beta and gamma chains. Here we examine the natural product of a novel fibrinogen alpha chain transcript bearing a separate open reading frame that supplies the missing C-terminal homology to the other chains. Additional splicing leads to the use of this extra sequence as a sixth exon elongating the alpha chain by 35%. Since the extended alpha chain (alpha E) is assembled into fibrinogen molecules and its synthesis is enhanced by interleukin-6, it suggests participation in both the acute phase response and normal physiology.
Biochemistry 1992 Dec 08
PMID:Carboxy-terminal-extended variant of the human fibrinogen alpha subunit: a novel exon conferring marked homology to beta and gamma subunits. 145 96

Rheumatoid synovial T lymphocytes were investigated for the presence of mRNA for the cytokines interleukin-2, -3, -4, -6, interferon-gamma, the interleukin-2 receptor (CD25) and the proto-oncogene c-myc. The isolated RNAs were analysed by dot blot and Northern blot hybridization. Our results show that synovial T lymphocytes from patients with rheumatoid arthritis (n = 12) had spontaneous in vivo gene transcription of interleukin-2 (93%), interleukin-4 (67%), interleukin-6 (92%), interleukin-2 receptor (92%) and the proto-oncogene c-myc (67%). Only a few of the RA patients had synovial T cells with increased expression of mRNA for interleukin-3 (25%) and interferon-gamma (25%). The amounts of mRNA for the various cytokines and activation molecules produced by the rheumatoid synovial T lymphocytes were in most instances comparable to those of normal peripheral blood T lymphocytes activated in vitro by the mitogen phytohaemagglutinin. The data thus indicate that the synovial T lymphocytes are activated in vivo in the majority of rheumatoid arthritis patients.
Scand J Immunol 1992 Dec
PMID:Spontaneous in vivo gene transcription of interleukin-2, interleukin-3, interleukin-4, interleukin-6, interferon-gamma, interleukin-2 receptor (CD25) and proto-oncogene c-myc by rheumatoid synovial T lymphocytes. 146 23

Sixteen vitreous and paired serum samples from 13 patients with proliferative diabetic retinopathy, vitreous samples from seven cadaveric control subjects, and aqueous humor samples from 15 normal control subjects were assayed for the cytokines interleukin-1, tumor necrosis factor-alpha, interleukin-6, and interferon-gamma. Interleukin-6 was detected in 15 of 16 vitreous samples (94%) from diabetic patients, but it was not detected in any of the aqueous humor samples. Vitreous interleukin-6 levels positively correlated with ocular disease activity. Interleukin-1 was detected in seven of 16 vitreous samples (44%) and in four of ten aqueous humor samples (40%), whereas tumor necrosis factor-alpha and interferon-gamma were never detected in vitreous or aqueous fluid. Serum samples from diabetic patients and control subjects contained comparable low levels of interleukin-6. Interleukin-1, tumor necrosis factor-alpha, and interferon-gamma were not found in any of the sera. Because interleukin-6 can function as B-cell differentiation factor, this cytokine may have a role in immunoglobulin deposition in the ocular tissues and in the immunopathologic characteristics of proliferative retinopathy.
Am J Ophthalmol 1992 Dec 15
PMID:Cytokines in the vitreous of patients with proliferative diabetic retinopathy. 146 43

Cytokines are known to play an important role in host defense by regulating the function, growth, and differentiation of the cells of the immune system. We hypothesize that, in the tumor microenvironment, tumor cells and resident tissue cells (e.g., fibroblasts) also produce cytokines that may regulate the local immune response to tumors. Initially, homogenates of eight head and neck squamous cell carcinomas (HNSCC) were assayed for the presence of interleukin-1 (IL-1), interleukin-4 (IL-4), interleukin-6 (IL-6), and granulocyte-macrophage colony-stimulating factor (GM-CSF) to establish the presence of these cytokines in the tumors in vivo. We detected IL-1 in all tumor homogenates and IL-4, IL-6, and GM-CSF in some homogenates. To assess the ability of HNSCC to produce these cytokines, supernatants of short-term primary cultures of HNSCC were assayed for the same cytokines. No IL-1 was detected, although baseline levels of IL-4, IL-6, and GM-CSF were present. However, the stimulation of primary tumor cultures with exogenous IL-1 induced or significantly enhanced production of IL-4 (p < 0.01), IL-6 (p < 0.001), and GM-CSF (p < 0.02). These results support our hypothesis that HNSCC secrete cytokines that may influence the response of local immune cells. Our data also suggest that IL-1 may have a central role in regulating the local immune response through the enhancement or induction of cytokine production by tumor and/or resident tissue cells.
Am J Surg 1992 Dec
PMID:Cytokine expression by head and neck squamous cell carcinomas. 146 1

Macrophages elaborate both effector and regulatory immune functions. It was hypothesised that tumours can exert a local alteration of macrophage function. Murine peritoneal macrophage-derived cytokines were assayed in the presence and absence of cells, cytosol fractions or conditioned media (TCCM) from established murine tumour lines. Interleukin-1 beta, interleukin-6 and tumour necrosis factor-alpha activities were significantly inhibited by tumour cells or their products, as were the corresponding recombinant human cytokines. Intracellular protein kinase C activation was also measured and was significantly inhibited by murine TCCM, thus suggesting one possible site of inhibitor action. Data analyses indicate that the inhibitory factor(s) is probably not an already well-characterised macrophage inhibitor.
FEMS Microbiol Immunol 1992 Dec
PMID:Tumour cell inhibition of macrophage cytokine activity. 146 2

Granulocyte/macrophage colony stimulating factor (GM-CSF) is a hematopoietic growth factor that stimulates a wide range of myeloid hematopoietic cells; RNAs coding for many oncogenes and cytokines including GM-CSF have a very short half-life. The motif of AUUUA is a highly conserved sequence in the 3'untranslated regions (3'UTR) of these transcripts and is repeated a number of times in these short-lived cytokines and oncogenes. These sequences play a major role in controlling stability of these transcripts. Human cancer cells were transfected with a chimeric rabbit beta-globin gene linked to either a 58 bp sequence of the AT-rich region from GM-CSF or a control sequence. We have found that irradiation stimulates accumulation of GM-CSF, interleukin-6 (IL-6), and IL-1 beta RNAs. In addition, this accumulation of GM-CSF was at least, in part, a result of increased stabilization of GM-CSF transcripts. Further experiments showed that irradiation increased levels of the chimeric beta-globin transcripts containing AUUUA sequences from GM-CSF, but not those containing the control sequences. Our results suggest that irradiation increases expression of GM-CSF RNA and that posttranscriptional stabilization requiring AUUUA sequences probably is in part one of the mechanisms producing the increased levels of GM-CSF RNA by irradiation.
Biochem Biophys Res Commun 1992 Dec 15
PMID:Irradiation increases levels of GM-CSF through RNA stabilization which requires an AU-rich region in cancer cells. 147 71

Plasma Interleukin-6 (IL-6) level was measured in 60 patients with disseminated intravascular coagulation (DIC). Plasma IL-6 level was high in patients with DIC, and was particularly high in patients with multiple organ failure (MOF) or poor prognosis. Plasma IL-6 level correlated positively with C-reactive protein in patients without DIC, but not in those with DIC. The increased plasma IL-6 level observed in DIC patients suggests that activation of the immune system is involved in the progression of DIC and in the pathology of organ failure.
Rinsho Ketsueki 1992 Dec
PMID:[Plasma interleukin-6 in patients with disseminated intravascular coagulation]. 147 90

Interleukin-1 beta (Il-1 beta) and interleukin-1 alpha (Il-1 alpha) were shown to act as motility factors for the human breast carcinoma cell lines SK-BR-3 and ZR-75-1 in vitro. Both cytokines induced transition from the stationary to the motile phenotype (spreading). Il-1 beta stimulated translocation, shape change and random migration (chemokinesis) of SK-BR-3 cells as demonstrated by time-lapse video recordings and by a modified Boyden chamber assay. Interleukin-6 (Il-6) stimulated spreading of the SK-BR-3 cells; an additive effect with Il-1 beta on spreading and fast plasma membrane movements was evidenced. In the SK-BR-3 cell line, the signal transduction of Il-1 beta and Il-6 differed, since only the effect of Il-6 on spreading was sensitive to pertussis toxin. Both Il-1 beta and Il-6 required protein synthesis to stimulate spreading, since cycloheximide inhibited the effect of the cytokines. Induction of an autocrine loop of Il-6 in the SK-BR-3 cells by Il-1 beta was unlikely, since after stimulation with Il-1 beta, no induction of Il-6 activity was measured, nor was inhibition of stimulated spreading seen in the presence of an antiserum against Il-6. Addition of Il-8 or of an antiserum against Il-8 did not affect spreading. We concluded that Il-1 and Il-6 could act as motility factors for human breast carcinoma cells, in both an independent and an additive way.(ABSTRACT TRUNCATED AT 250 WORDS)
Eur J Cell Biol 1992 Dec
PMID:Interleukin-1 is a motility factor for human breast carcinoma cells in vitro: additive effect with interleukin-6. 149 10


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