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)

Ultrafiltration failure (UFF) continues to be a major complication of peritoneal dialysis (PD), particularly long-term PD. Continuous exposure to bioincompatible PD solutions causes inflammation of the peritoneal membrane, which progressively undergoes fibrosis and angiogenesis and, ultimately, UFF. There is emerging evidence that epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells (MCs) may play an important role in the failure of peritoneal membrane function. Submesothelial myofibroblasts originating from MCs through EMT and from activated resident fibroblasts participate in inflammatory responses, extracellular matrix accumulation, and angiogenesis. High glucose and glucose degradation products from PD solutions are responsible for production of transforming growth factor beta (TGFbeta) and vascular endothelial growth factor (VEGF) by MCs, which induce EMT. Leptin and receptor for advanced glycation end-products (AGEs) augment myofibroblastic conversion through the TGFbeta signaling system. A reduction in osmotic conductance in addition to increased solute transport causes UFF. This situation may be caused by loss of aquaporin (AQP) function and formation of the submesothelial fibrotic layer. During PD, AQP1 plays an essential role in water permeability and ultrafiltration (UF), modulating processes such as endothelial permeability and angiogenesis. During a hypertonic dwell, AQP1 mediates 50% of UF. Insufficient AQP1 function may be causative for inadequate UFF. A significant amount of evidence from animal studies now exists to show that mast cells communicate with fibroblasts and are implicated in fibrogenesis, angiogenesis, and UFF. However, it is not confirmed in human studies that mast cells contribute to the fibrosis seen in the peritoneum of PD patients. The patterns of UFF in PD patients depend on duration of treatment. Inherently high small-solute transport status is associated with hypoalbuminemia and a greater comorbidity index. However, most of the variability in peritoneal transport remains unexplained, pointing to the potential role of genetic factors. Gene polymorphisms associated with peritoneal membrane transport have been identified. Recent studies have shown that VEGF, interleukin-6, endothelial NO synthase, AGE receptor, and RAS gene polymorphisms are associated with transport properties in PD patients. Current insights into the mechanisms of UFF will provide rationales for new therapeutic strategies.
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PMID:Update on mechanisms of ultrafiltration failure. 1927 Feb

Although postpartum depression (PPD) is a common condition, it often goes undiagnosed and untreated, with devastating consequences for the woman's ability to perform daily activities, to bond with her infant and to relate to the infant's father. Leptin, a protein synthesised in the adipose tissue and involved in regulation of food intake and energy expenditure has been related to depressive disorders, but studies report conflicting results. The aim of this study was to evaluate the association between serum leptin levels at the time of delivery and the subsequent development of postpartum depression in women, using data from a population-based cohort of delivering women in Uppsala, Sweden. Three hundred and forty seven women from which serum was obtained at the time of delivery filled out at least one of three structured questionnaires containing the Edinburgh Scale for Postnatal Depression (EPDS) at five days, six weeks and six months after delivery. Mean leptin levels at delivery did not significantly differ between the 67 cases of PPD and the 280 controls. Using linear regression analysis and adjusting for maternal age, body-mass index, smoking, interleukin-6 levels, duration of gestation and gender of the newborn, the EPDS scores at six weeks and six months after delivery were found to be negatively associated with leptin levels at delivery (p<0.05). Serum leptin levels at delivery were found to be negatively associated with self-reported depression during the first six months after delivery. No such association was found concerning serum IL-6 levels at delivery. If these finding are replicated by other studies, leptin levels at delivery could eventually serve as a biological marker for the prediction of postpartum depression.
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PMID:Risk of postpartum depression in association with serum leptin and interleukin-6 levels at delivery: a nested case-control study within the UPPSAT cohort. 1942 31

Adipokines are polypeptides secreted in the adipose tissue in a regulated manner. While some of these molecules are expressed only by adipocytes, resident and infiltrating macrophages and components of the vascular stroma markedly contribute to expression of other adipokines. As a result, adipose tissue inflammation is associated with a modification in the pattern of adipokine secretion. Leptin, adiponectin, and resistin are the best-studied molecules in this class, but cytokines such as tumor necrosis factor or interleukin-6 are also secreted at high levels by the adipose tissue. Several other molecules have been recently identified and are actively investigated. Adipokines interfere with hepatic injury associated with fatty infiltration, differentially modulating steatosis, inflammation, and fibrosis. Several studies have investigated plasma levels of adiponectin in patients with nonalcoholic fatty liver disease, to establish correlations with the underlying state of insulin resistance and with the type and severity of hepatic damage. Hepatitis C is another disease where adipokines may represent a link between viral infection, steatosis, and metabolic disturbances. Identification of the mediators secreted by expanded adipose tissue and their pathogenic role is pivotal in consideration of the alarming increase in the prevalence of obesity and of the detrimental role that this condition exerts on the course of liver diseases.
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PMID:Adipokines in liver diseases. 1958 55

The purpose of this study was to assess the expression profile of genes with potential role in the development of insulin resistance (adipokines, cytokines/chemokines, estrogen receptors) in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placenta of pregnant women with gestational diabetes mellitus (GDM) and age-matched women with physiological pregnancy at the time of Caesarean section. qRT-PCR was used for expression analysis of the studied genes. Leptin gene expression in VAT of GDM group was significantly higher relative to control group. Gene expressions of interleukin-6 and interleukin-8 were significantly increased, whereas the expressions of genes for estrogen receptors alpha and beta were significantly reduced in SAT of GDM group relative to controls, respectively. We found no significant differences in the expression of any genes of interest (LEP, RETN, ADIPOR1, ADIPOR2, TNF-alpha, CD68, IL-6, IL-8, ER alpha, ER beta) in placentas of women with GDM relative to controls. We conclude that increased expression of leptin in visceral adipose depot together with increased expressions of proinflammatory cytokines and reduced expressions of estrogen receptors in subcutaneous fat may play a role in the etiopathogenesis of GDM.
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PMID:Expression of adipokines and estrogen receptors in adipose tissue and placenta of patients with gestational diabetes mellitus. 1968 37

Class-I cytokines represent a large group of molecules involved in different physiological processes including host defence, immune regulation, food intake, energy metabolism and, relevant for this review, reproduction. In this latter respect, here, we focus the attention on four of these molecules, specifically leptin, ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF) and interleukin-6 (IL-6). These cytokines present similar three-dimensional fold structure, interact with related class-I receptors, which are expressed in the same regions (i.e., hypothalamus), and activate similar intracellular pathways. Leptin and CNTF share functional similarities, by acting at hypothalamic and pituitary levels, and their receptors are colocalized in the arcuate and paraventricular nuclei of the hypothalamus. For both these molecules, no effect on GnRH migration has been described. LIF has also been shown to affect gonadotropin secretion and here we present the novel observation that it is also able to stimulate GnRH secretion in vitro. Moreover, in the mouse, LIF is prenatally expressed in nasal regions where GnRH neurons originate and start their migration, and in vitro it stimulates intrinsic cell motility and directional migration. The role of the prototypical cytokine, IL-6, on the GnRH-LH axis is not fully clear and additional information seem necessary to better clarify this aspect. In conclusion, the data here discussed suggest that this family of cytokines appears to participate to the complex control of the reproductive function by affecting the development and function of the hypothalamus-pituitary system at different ontogenic times and anatomical sites.
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PMID:Leptin, ciliary neurotrophic factor, leukemia inhibitory factor and interleukin-6: class-I cytokines involved in the neuroendocrine regulation of the reproductive function. 1975 Nov 93

It may be that resistance exercise can be used to prevent the degenerative processes and inflammation associated with ageing. Thus, the aim of the present study was to evaluate the effects of resistance training on cytokines, leptin, resistin, and muscle strength in post-menopausal women. Thirty-five sedentary women (mean age 63.18 years, s = 4.8; height 1.64 m, s = 0.07; body mass 57.84 kg, s = 7.70) were recruited. The 16 weeks of periodized resistance training consisted of two weekly sessions of three sets of 6-14 repetition maximum. Maximal strength was tested in bench press, 45 degrees leg press, and arm curl. Plasma tumour necrosis factor-alpha, interleukin-6, interleukin-15, leptin, and resistin were determined by enzyme-linked immunosorbent assay. Maximal strength on all measures was increased after 16 weeks. There were minor or no modifications in tumour necrosis factor-alpha and interleukin-15. Interleukin-6 was decreased 48 h after compared with baseline and declined after 16 weeks. Leptin decreased 24 h after compared with baseline and was reduced at baseline and 48 h after compared with pre-training. There was a decrease in resistin after 24 and 48 h compared with baseline and a decline in baseline and immediately after levels compared with pre-training. A possible explanation of the results of the present study is a lower production of pro-inflammatory cytokines by the innate immune system. Periodized resistance training seems to be an important intervention to reduce systemic inflammation in this population.
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PMID:Effects of resistance training on resistin, leptin, cytokines, and muscle force in elderly post-menopausal women. 1996 92

Obesity has been implicated in several inflammatory diseases and in different types of cancer. Chronic inflammation induced by exposure to ultraviolet (UV) radiation has been implicated in various skin diseases, including melanoma and nonmelanoma skin cancers. As the relationship between obesity and susceptibility to UV radiation-caused inflammation is not clearly understood, we assessed the role of obesity on UVB-induced inflammation, and mediators of this inflammatory response, using the genetically obese (leptin-deficient) mouse model. Leptin-deficient obese (ob/ob) mice and wild-type counterparts (C57/BL6 mice) were exposed to UVB radiation (120 mJ/cm(2)) on alternate days for 1 month. The mice were then euthanized and skin samples collected for analysis of biomarkers of inflammatory responses using immunohistochemistry, western blotting, ELISA and real-time PCR. Here, we report that the levels of inflammatory responses were higher in the UVB-exposed skin of the ob/ob obese mice than those in the UVB-exposed skin of the wild-type non-obese mice. The levels of UVB-induced cyclooxygenase-2 expression, prostaglandin-E(2) production, proinflammatory cytokines (i.e., tumor necrosis factor-alpha, interleukin-1beta, interleukin-6), and proliferating cell nuclear antigen and cell survival signals (phosphatidylinositol-3-kinase and p-Akt-Ser(473)) were higher in the skin of the ob/ob obese mice than the those in skin of their wild-type non-obese counterparts. Compared with the wild-type non-obese mice, the leptin-deficient obese mice also exhibited greater activation of NF-kappaB/p65 and fewer apoptotic cells in the UVB-irradiated skin. Our study suggests for the first time that obesity in mice is associated with greater susceptibility to UVB-induced inflammatory responses and, therefore, obesity may increase susceptibility to UVB-induced inflammation-associated skin diseases, including the risk of skin cancer.
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PMID:Leptin deficiency-induced obesity exacerbates ultraviolet B radiation-induced cyclooxygenase-2 expression and cell survival signals in ultraviolet B-irradiated mouse skin. 2057 Jun 90

Obesity is considered the most important risk and prognostic factor for estrogen-dependent breast cancer in postmenopausal women. Adipokines, in particular leptin, are at the center of the etiopathogenetic mechanisms by which obesity and related metabolic disorders influence breast cancer risk and its prognosis. The present prospective observational study aims to investigate the relationship between body mass index (BMI), serum levels of leptin and proinflammatory cytokines, and breast cancer prognostic factors. In the study, 98 postmenopausal and 82 premenopausal patients with ER-positive breast cancer participated. During the same study period, 221 control subjects were simultaneously recruited. Women underwent baseline measurements pre-operatively, before any surgical and systemic treatments. Pathologic characteristics of tumors were abstracted from pathology reports. Leptin and proinflammatory cytokines were assayed in stored fasting blood specimens. In postmenopausal breast cancer patients, BMI, leptin, and interleukin-6 significantly correlated with pathological tumor classification (pT) and TNM stage. Multivariate regression analysis showed that BMI and leptin, but not interleukin-6, were independent predictive variables of pT and TNM stage. Our results seem to suggest a twofold role of leptin in the etiopathogenesis of postmenopausal estrogen-positive breast cancer. Indeed, leptin reflects the total amount of fat mass, which correlates to aromatase activity and subsequent estrogens levels. Further studies are warranted to clarify the role of leptin and interleukin-6 in breast carcinogenesis and identify new therapeutic options, beyond the use of aromatase inhibitors, acting selectively on adipokine-driven pathways.
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PMID:Correlation of body mass index and leptin with tumor size and stage of disease in hormone-dependent postmenopausal breast cancer: preliminary results and therapeutic implications. 2033 29

A growing body of evidence suggests that chronic inflammation contributes to cancer development and progression. Tumor-derived immunoinflammatory cytokines help tumor cells escape immune control and limit the success of immunotherapy. Leptin has been proven to promote cancer progression by inducing cancer cell proliferation and invasion. However, the proinflammatory effects of leptin on lung cancer cells have not yet been fully elucidated. In this study, we demonstrated that human lung cancer A549 and H157 cells express leptin receptors Ob-Ra and Ob-Rb, and that leptin stimulation increases the production of immunoinflammatory cytokines: vascular endothelial growth factor (VEGF), interleukin-6 (IL-6) and prostaglandin (PGE2). Moreover, leptin stimulation activated the JAK/STAT3, PI3K/AKT and MEK1/2 signaling pathways, which contributed to VEGF, IL-6 and PGE2 production. Besides increasing immunoinflammatory cytokines, leptin also protected human lung cancer cells from tumor necrosis factor-related apoptosis-induced ligand-mediated cytotoxic death. Thus, we conclude that leptin promotes the immune escape of lung cancer by inducing proinflammatory cytokines and resistance to apoptosis.
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PMID:Leptin promotes the immune escape of lung cancer by inducing proinflammatory cytokines and resistance to apoptosis. 2147 28

The discovery of adipocytokines, products of adipose tissue, has been a turning point in the understanding of metabolic disorders. Historically considered as a passive depot of energy, adipose tissue has become an important active participant and adipocytokines crucial mediators of its metabolic role. Among a number of adipose tissue products, leptin and adiponectin are exclusively secreted by adipocytes. Leptin regulates energy homeostasis and interferes with several neuroendocrine and immune functions. Adiponectin is an intriguing adipocytokine with its serum level inversely correlated with fatness. It has been related to enhanced insulin sensitivity, anti-inflammatory and anti-atherogenic actions. Recent investigations have also emphasized the important role of resistin, visfatin, retinol binding protein 4, and of a whole list of cytokines like interleukin-6, tumor necrosis factor a, plasminogen activator inhibitor-1, or a chemokine, monocyte chemoattractant protein-1. The fact that secretory balance of adipose tissue in obesity is shifted towards the proinflammatory spectrum has supported the hypothesis on the development of dysfunctional adipose tissue in these circumstances. It contributes to the state of chronic inflammation and insulin resistance, and it seems to be a fundamental link between obesity and atherosclerosis.
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PMID:[Adipocytokines as mediators of metabolic role of adipose tissue]. 2168 8


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