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)

Langerhans' cell histiocytosis (LCH) is a clonal proliferation of Langerhans cells (LC) showing histologically an abundant reactive infiltrate composed of macrophages and lymphocytes, as well as eosinophilic and neutrophilic granulocytes. Rosai-Dorfman disease (RDD) shows a sinusoidal accumulation of large histiocytic cells with an immunophenotype similar to LC of LCH. The histological picture of LCH is reminiscent of an inflammatory disorder and LC may produce cytokines and are influenced by these soluble factors. This study set out to establish the monokine expression pattern in LCH in comparison with those of RDD; dermatopathic lymphadenopathy, which also shows a proliferation of S100-positive dendritic cells; and LC in normal skin specimens. Isotopic in situ hybridization was used for the detection of transcripts of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1 beta, in some cases combined with immunohistology for the S100 protein or CD68. In all 11 tissue samples from eight patients, LC of LCH expressed TNF-alpha; in two cases IL-1 beta transcripts were additionally noted in some LC, whereas IL-6 was found in reactive cells. Large histiocytic cells of RDD expressed all three monokines, whereas minimal or no expression of these cytokines could be detected in interdigitating reticulum cells in dermatopathic lymphadenopathy. In two out of five normal skin samples, only TNF-alpha specific signals were observed in LC. These data suggest that histologically different lesions of the histiocytic/dendritic cell system display distinct cytokine profiles. The expression of monokines, which have been demonstrated to influence various functions of epidermal LC, may play a role in the pathogenesis of LCH. Systemic symptoms in RDD may be related to enhanced production of monokines in these lesions.
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PMID:Monokine expression in Langerhans' cell histiocytosis and sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) 912 Jul 35

The population of folliculo-stellate (FS) cells of the rat anterior pituitary has been shown to be ultrastructurally and immunohistochemically heterogeneous. Based on the overlap of ultrastructural characteristics, the localization in the anterior pituitary and the co-expression within the same cel of the S-100 protein (a marker for FS cells) and MHC-class II determinants (an immune marker) we concluded that a partial overlap exists between the population of FS cells and the monocyte-derived dendritic cells (DC). In this report we describe that interleukin-6 (IL-6) immunoreactivity was found in situ in stellate cells of the rat, mouse and human anterior pituitary at a very low density (< 1% of the cells); the topography was reminiscent of the distribution of FS cells. In the present study we also analyse three different pituitary cell separation methods, in order to study the functional heterogeneity of the FS cells in vitro, and to verify whether functionally distinct subpopulations exist within the FS cell group. Production of bioactive IL-6 was measured in conditioned media of rat anterior pituitary cells separated by (i) bovine serum albumin (BSA) gradient sedimentation at 1 g, (ii) Nycodenz gradient and (iii) a magnetic cell separation (MACS) technique. Production of bioactive IL-6 by cell cultures of 1 to 4 days was correlated with the proportional number of S100 immunoreactive and S100 producing cells, but was not correlated with the proportional number of MHC-class II expressing (OX6-positive) dendritic cells (DC). The distribution pattern of OX6-positive DC was found to partly overlap with the distribution pattern of S100-positive cells in the BSA gradient. Co-sedimentation of S100-positive FS cells and MHC-class II-expressing DC was not restricted to the top fractions of the BSA gradient, but was also found in the low density Nycodenz fraction. MACS separation of the rat anterior pituitary cells resulted into a population enriched in OX6 and OX62 positive DC and a population devoid of such cells, while S100+ cells were equally divided into these two subpopulations. Although there was a significantly decreased production of IL-6 as compared to that of an original pituitary cell population, both MACS separated populations were equal in IL-6 production. The diminution in IL-6 production in both populations may be the result of an impediment of paracrine communication due to the MACS separation into these two populations. Our data also show that a subpopulation of FS cells was capable of stimulating T cell proliferation in vitro. Concomitantly with the distribution pattern of S100- and OX6-immunoreactive cells in the BSA and Nycodenz gradient fractions, we found a similar pattern of stimulation of T cell proliferation. Unlike the IL-6 production pattern, the T cell stimulating capacity was present in the MHC-class II-enriched cell population but absent in the MHC-class II-depleted cell population. These findings-together with earlier in situ histochemical data-suggest that there is an OX6+ S100- subpopulation of FS cells in the anterior pituitary that in itself is capable of stimulating T cell proliferation in vitro, and acts as lymphoid DC. There is also an S100+ OX6- population that is unable to stimulate T cell proliferation in vitro. Both populations are able to produce IL-6, but probably need stimuli from other subpopulations of pituitary cells (or exogeneous stimuli) to produce maximal amounts of IL-6.
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PMID:Heterogeneity of pituitary folliculo-stellate cells: implications for interleukin-6 production and accessory function in vitro. 902 37

Pituitary folliculostellate (FS) cells are usually located between the secretory cells in the anterior pituitary, and they produce many peptides that exert a paracrine effect on hormone-producing pituitary cells. Previous approaches have been unsuccessful in obtaining homogeneous populations of FS cells. We used a combination of immunostaining with S100 protein followed by laser capture microdissection (Immuno-LCM) to obtain purified populations of rat FS cells. These cells were analyzed along with a mouse FS cell line (TtT/GF) by RT-PCR for gene expression. RT-PCR analyses showed that both FS cell populations expressed the mRNAs for glial fibrillary acidic protein, S100 protein, transforming growth factor-beta1 (TGFbeta1), TGFbeta receptor, interleukin-6, leptin, leptin receptor, pituitary adenylate cyclase-activating polypeptide (PACAP), and PACAP receptors. Both FS cell populations were negative for PRL, GH, and POMC, supporting the homogeneity of the rat FS cell population. TGFbeta1, but not PACAP-38, treatment stimulated cell proliferation in both FS cell populations. TGFbeta1 increased leptin, but not interleukin-6, mRNA expression in rat FS cells. However, TGFbeta1 inhibited leptin RNA expression in the TtT/GF cell line, as shown by RT-PCR and Northern blot analysis. These results indicate that 1) homogeneous populations of FS cells can be prepared by Immuno-LCM; 2) TGFbeta1 stimulates the proliferation of normal rat FS cells and the TtT/GF cell line; and 3) the effects of TGFbeta1 to stimulate leptin mRNA expression in rat FS cells but inhibit leptin mRNA expression in TtT/GF cells probably reflect alterations in signal transduction in the TtT/GF cell line.
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PMID:Analysis of homogeneous populations of anterior pituitary folliculostellate cells by laser capture microdissection and reverse transcription-polymerase chain reaction. 1131 32

Receptor for advanced glycation end-products (RAGE), and two of its ligands, AGE and EN-RAGEs (members of the S100/calgranulin family of pro-inflammatory cytokines), display enhanced expression in slowly resolving full-thickness excisional wounds developed in genetically diabetic db+/db+ mice. We tested the concept that blockade of RAGE, using soluble(s) RAGE, the extracellular ligand-binding domain of the receptor, would enhance wound closure in these animals. Administration of sRAGE accelerated the development of appropriately limited inflammatory cell infiltration and activation in wound foci. In parallel with accelerated wound closure at later times, blockade of RAGE suppressed levels of cytokines; tumor necrosis factor-alpha; interleukin-6; and matrix metalloproteinases-2, -3, and -9. In addition, generation of thick, well-vascularized granulation tissue was enhanced, in parallel with increased levels of platelet-derived growth factor-B and vascular endothelial growth factor. These findings identify a central role for RAGE in disordered wound healing associated with diabetes, and suggest that blockade of this receptor might represent a targeted strategy to restore effective wound repair in this disorder.
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PMID:Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice. 1148 96

Concentrations of the calcium-binding proteins of the S100 family, myeloid-related proteins 8 and MRP 14 (MRP8/14), are elevated in chronic infections, yet the role of these proteins is not clearly defined. Using commercial and developed enzyme immunoassays, we assayed for MRP8/14 in sterile-filtered abscess fluid from tissue-cage-implanted rats and rabbits. Staphylococcus aureus abscesses were created 6 weeks after the intraperitoneal implantation of tissue cages. Leukocytes, bacteria, and non-protein-bound calcium and zinc were measured in the infection exudate at day 3 or 5 of infection and after 8 days of treatment with antimicrobials beta-lactams (18 rabbits, 35 rats) and fluoroquinolone-rifampin (6 rabbits). Half of the infected rats were depleted of neutrophils; these rats exhibited significantly lower MRP 8/14 concentrations on all days sampled, regardless of the level of infection. The level of abscess MRP 8/14 is high early in the course of infection but decreases with effective antimicrobial treatment by as much as 100-fold. Thirty-day-old abscesses with log 6 bacterial counts and low neutrophil counts showed low concentrations of MRP 8/14 in these models. In abscess fluid, interleukin-6, as a representative marker of inflammation, correlated with MRP8/14, whereas ionized calcium and zinc did not. Our data suggest that infection and inflammation are not equal stimuli for MRP 8/14. The neutrophil appears to be the main source of MRP8/14 in this model.
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PMID:Calcium-binding proteins MRP 8 and 14 in a Staphylococcus aureus infection model: role of therapy, inflammation, and infection persistence. 1257 47

The SJL mouse is a model for human dysferlinopathy (limb-girdle muscular dystrophy type 2B and Miyoshi myopathy). We used cDNA microarrays to compare the expression profiles of 10,012 genes in control and SJL quadriceps femoris muscles in order to find genes involved in the degeneration and regeneration process and in dysferlin's functional network. Many genes involved in the process of muscle regeneration are observed to be up-regulated in SJL mice, including cardiac ankyrin repeated protein (CARP), Neuraminidase 2, interleukin-6, insulin-like growth factor-2 and osteopontin. We found the upregulation of S100 calcium binding proteins, neural precursor cell expressed, developmentally down-regulated gene 4-like (NEDD4L) with C2 domain, and intracellular protein traffic associated proteins (Rab6 and Rab2). These proteins have the potential to interact with dysferlin. We must reveal some other molecules which may work with dysferlin in order to clarify the pathological network of dysferlinopathy. This process may lead to future improvements in the therapy for human dysferlinopathy.
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PMID:Expression profiling with progression of dystrophic change in dysferlin-deficient mice (SJL). 1581 52

Although neonatal hypoxic-ischemic encephalopathy is a common cause of childhood developmental disability, its timing, duration, and outcomes are poorly defined. Biomarkers serve as surrogates for disease injury, evolution, and outcome, but no tissue biomarker in routine clinical use can help predict outcomes in term newborn encephalopathy. We reviewed biomarkers in human term neonatal encephalopathy, to determine if current biomarkers are strong enough for clinical use as predictors of outcomes. A comprehensive search of databases identified 110 publications that met our inclusion criteria, i.e., (1) newborns at >36 weeks; (2) neonatal encephalopathy as defined by the American College of Obstetrics and Gynecology; (3) the use of a serum, urine, or cerebrospinal fluid biomarker; and (4) reported outcomes beyond age 12 months. Of those 110 publications, 22 reported outcomes beyond age 12 months. In single reports, urine lactate (P < 0.001), first urine S100 (P < 0.0001), cord-blood interleukin-6 (P = 0.02), serum nonprotein-bound iron (P < 0.001), serum CD14 cell NFkappaB activation (P = 0.014), serum interleukin-8 (P = 0.03), and serum ionized calcium (P = 0.001) were potential predictors of death or abnormal outcomes. A meta-analysis identified serum interleukin-1b (P = 0.04, n = 3), serum interleukin-6 (P = 0.04, n = 2), cerebrospinal fluid neuron-specific enolase (P = 0.03, n = 3), and cerebrospinal fluid interleukin-1b (P = 0.003, n = 2) as putative predictors of abnormal outcomes in survivors, when measured before age 96 hours. Several serum, urine, and cerebrospinal fluid biomarkers of term neonatal encephalopathy may provide important information regarding long-term outcomes. None, however, were studied extensively enough to warrant routine clinical use. Validation of these markers, either alone or in combination, is required in the development of viable therapeutic interventions.
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PMID:Systematic review of biomarkers of brain injury in term neonatal encephalopathy. 1921 35

Immune activation represents an adaptive reaction triggered by both noxious exogenous (microbes) and endogenous [high mobility group box-1 protein (HMGB1), S100 calcium binding proteins] inducers of inflammation. Cell stress or necrosis lead the release of HMGB1 and S100 proteins in the extracellular compartment where they act as damage-associated molecular pattern molecules (or alarmins) by engaging the receptor for advanced glycation end-products (RAGE). Although the biology of RAGE is dictated by the accumulation of damage-associated molecular pattern molecules at sites of tissue injury, the role of RAGE in mediating antenatal fetal injury remains unknown. First, we studied the relationships at birth between the intensity of human fetal inflammation and sRAGE (an endogenous RAGE antagonist), HMGB1, and S100beta protein. We found significantly lower sRAGE in human fetuses that mounted robust inflammatory responses. HMGB1 levels correlated significantly with levels of interleukin-6 and S100beta in fetal circulation. We then evaluated the levels and areas of tissue expression of RAGE, HMGB1, and S100beta in specific organs of mouse fetuses on E16. Using an animal model of endotoxin-induced fetal damage and preterm birth, we determined that inflammation induces a significant change in expression of RAGE and HMGB1, but not S100beta, at sites of tissue damage. Our findings indicate that RAGE and HMGB1 may be important mediators of cellular injury in fetuses delivered in the setting of inflammation-induced preterm birth.
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PMID:Characterization of RAGE, HMGB1, and S100beta in inflammation-induced preterm birth and fetal tissue injury. 1967 74

Juvenile idiopathic arthritis is a heterogeneous group of diseases characterised by arthritis of unknown origin with onset before age of 16 years. Pivotal studies in the past 5 years have led to substantial progress in various areas, ranging from disease classification to new treatments. Gene expression profiling studies have identified different immune mechanisms in distinct subtypes of the disease, and can help to redefine disease classification criteria. Moreover, immunological studies have shown that systemic juvenile idiopathic arthritis is an acquired autoinflammatory disease, and have led to successful studies of both interleukin-1 and interleukin-6 blockade. In other forms of the disease, synovial inflammation is the consequence of a disturbed balance between proinflammatory effector cells (such as T-helper-17 cells), and anti-inflammatory regulatory cells (such as FOXP3-positive regulatory T cells). Moreover, specific soluble biomarkers (S100 proteins) can guide individual treatment. Altogether these new developments in genetics, immunology, and imaging are instrumental to better define, classify, and treat patients with juvenile idiopathic arthritis.
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PMID:Juvenile idiopathic arthritis. 2168 84

We present the case of an 81-year-old man with primary clear cell sarcoma (CCS) of the pubic bone with an associated aggressive clinical course. The patient's laboratory tests showed marked leukocytosis, elevated levels of C-reactive protein and multiple cytokines, including interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF). Histological examination showed monomorphic small cells predominantly arranged as a diffuse sheet with morphological features of a small round cell tumor (SRCT). Immunohistochemical staining indicated that the tumor cells were positive for HMB45, S100, Melan A, IL-6, IL-6 receptor, G-CSF, and G-CSF receptor and negative for cytokeratin (AE1/AE3) and epithelial membrane antigen. To the best of our knowledge, this is the first case report of aggressive primary CCS of the pubic bone with features of SRCT showing the production and co-expression of multiple cytokines and their receptors. Thus, we suggest that proliferation through an IL-6- and G-CSF-associated autocrine mechanism may play an important role in the aggressive clinical course and poor prognosis of some CCSs showing features of SRCT.
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PMID:Co-expression of multiple cytokines and their receptors in primary clear cell sarcoma of the pubic bone with features of a small round cell tumor. 2305 34


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