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)

We here examined the role of the interleukin-6 (IL-6) family of cytokines in endothelin-1 (ET-1)-induced hypertrophic responses using cultured cardiac myocytes of neonatal rats. ET-1 induced expression of IL-6 and leukemia inhibitory factor (LIF) genes. ET-1-induced LIF gene expression was abolished by inhibition of protein kinase C activity. ET-1 activated the promoter of atrial natriuretic peptide and beta-type myosin heavy chain genes through the tyrosine kinase pathway and IL-6 receptor gp130. These results suggest that the IL-6 family of cytokines mediates ET-1-induced expression of some fetal genes in cardiac myocytes.
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PMID:Endothelin-1 induces expression of fetal genes through the interleukin-6 family of cytokines in cardiac myocytes. 1045 39

Cardiac myxomas are benign tumors which sometimes secrete interleukin-6 (IL-6), however, the pathogenesis and the IL-6 secreting cells are not clear. There are vascular myosin heavy chain isoforms; SM2 expression is specific to mature smooth muscle cells, while SMemb is a nonmuscle-type isoform which is expressed in immature mesenchyme cells. We hypothesized that immature mesenchyme cells play pivotal roles in the secretion of IL-6; we studied these expression in resected samples of myxoma. SMemb expression was increased but SM2 expression was not in the channels of myxoma. Increased IL-6 transcription was observed in the SMemb expressing cells in the channel. Therefore, mesenchyme cells with immature phenotype in the channel play pivotal roles of inflammation and pathogenesis of cardiac myxoma.
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PMID:In situ interleukin-6 transcription in embryonic nonmuscle myosin heavy chain expressing immature mesenchyme cells of cardiac myxoma. 1073 5

Sarcopenia is a term utilized to define the loss of muscle mass and strength that occurs with aging. Sarcopenia is believed to play a major role in the pathogenesis of frailty and functional impairment that occurs with old age. Progressive muscle wasting occurs with aging. The prevalence of clinically significant sarcopenia is estimated to range from 8.8% in young old women to 17.5% in old old men. Persons who are obese and sarcopenic (the "fat frail") have worse outcomes than those who are sarcopenic and non-obese. There is a disproportionate atrophy of type IIa muscle fibers with aging. There is also evidence of an age-related decrease in the synthesis rate of myosin heavy chain proteins, the major anabolic protein. Motor units innervating muscle decline with aging, and there is increased irregularity of muscle unit firing. There are indications that cytokines-especially interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6-play a role in the pathogenesis of sarcopenia. Similarly, the decline in anabolic hormones-namely, testosterone, dehydroepiandrosterone growth hormone, and insulin-like growth factor-I-is also implicated in the sarcopenic process. The role of the physiologic anorexia of aging remains to be determined. Decreased physical activity with aging appears to be the key factor involved in producing sarcopenia. An increased research emphasis on the factors involved in the pathogenesis of sarcopenia is needed.
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PMID:Sarcopenia. 1128 18

The purpose of this study was to examine the time-course and relationships of technetium-99m (99mTc) neutrophils in muscle, interleukin-6 (IL-6), myosin heavy chain fragments (MHC), eccentric torque, and delayed onset muscle soreness (DOMS) following eccentric exercise in humans. Twelve male subjects completed a pre-test DOMS questionnaire, performed a strength test and had 100 ml blood withdrawn for analysis of plasma IL-6 and MHC content. The neutrophils were separated, labelled with 99mTc, and re-infused into the subjects immediately before the exercise. Following 300 eccentric repetitions of the right quadriceps muscles on an isokinetic dynamometer, the subjects had 10 ml of blood withdrawn with repeated the eccentric torque exercise tests and DOMS questionnaire at 0, 2, 4, 6, 20, 24, 48, 72 h, and 6 and 9 days. Bilateral images of the quadriceps muscles were taken at 2, 4, and 6 h. Computer analysis of regions of interest was used to determine the average count per pixel. The 99mTc neutrophils and IL-6 increased up to 6 h post-exercise (P < 0.05). The neutrophils were greater in the exercised muscle than the non-exercised muscle (P < 0.01). The DOMS was increased from 0 to 48 h, eccentric torque decreased from 2 to 24 h, and MHC peaked at 72 h post-exercise (P < 0.001). Significant relationships were found between IL-6 and 2 h and DOMS at 24 h post-exercise (r = 0.68) and assessment of the magnitude of change between IL-6 and MHC (r = 0.66). These findings suggest a relationship between damage to the contractile proteins and inflammation, and that DOMS is associated with inflammation but not with muscle damage.
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PMID:Markers of inflammation and myofibrillar proteins following eccentric exercise in humans. 1132 Jun 33

Aging is associated with decreased skeletal muscle mass and function. These changes are thought to derive, in part, from a reduction in skeletal muscle protein synthesis. Although some studies have shown reduced postabsorptive muscle protein synthesis with age in humans, recent studies have failed to find an age effect. In addition to this disparity, few studies have attempted to characterize the hormonal factors that may contribute to changes in protein synthesis. Thus we examined the effect of age on skeletal muscle protein metabolism, with a specific emphasis on myosin heavy chain (MHC) protein, and the relationship of protein synthesis rates to plasma hormone levels. We measured body composition, muscle function, muscle protein synthesis, MHC and actin protein content, MHC isoform distribution, and plasma concentrations of cytokines and insulin-like growth factor-I (IGF-I) in 7 young [29 +/- 2 (SE) yr] and 15 old (72 +/- 1 yr; P < 0.01) volunteers. Mixed-muscle (-19%; P = 0.11), MHC (-22%; P = 0.08), and nonmyofibrillar (-17%; P = 0.10) protein synthesis all tended to be lower in old volunteers. Old volunteers were characterized by increased circulating tumor necrosis factor-alpha receptor II (P < 0.05) and reduced IGF-I (P < 0.01). In addition, plasma C-reactive protein, interleukin-6, and tumor necrosis factor-alpha receptor II concentrations were negatively related to mixed-muscle and MHC protein synthesis rates (range of r values: -0.422 to -0.606; P < 0.05 to <0.01). No differences in MHC or actin protein content were found. Old volunteers showed reduced (P < 0.05) MHC IIx content compared with young volunteers but no differences in MHC I or IIa. Our data show strong trends toward reduced postabsorptive muscle protein synthesis with age. Moreover, reduced muscle protein synthesis rates were related to increased circulating concentrations of several markers of immune activation.
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PMID:Age-related differences in skeletal muscle protein synthesis: relation to markers of immune activation. 1561 83

Leukemia inhibitory factor (LIF) is a multifunctional cytokine belonging to the interleukin-6 family and has been shown to stimulate regeneration of injured skeletal muscle. Although LIF has been shown to stimulate muscle cell proliferation, its precise role in differentiation is unclear. Thus, we examined the effect of LIF on the differentiation of cultured C2C12 myoblast cells. In this study, we used both non-glycosylated LIF expressed in bacteria and glycosylated LIF secreted from NIH3T3 cells infected with Ad-LIF. Both non-glycosylated and glycosylated LIF blocked differentiation of myoblasts as measured by expression of myosin heavy chain and myotube formation. Treatment of myoblasts with LIF induced phosphorylation of ERK, and the LIF-induced inhibitory effect on myogenesis was blocked by pretreatment with U0126, a specific MEK inhibitor, and transient transfection with dominant negative (DN)-MEK1. In contrast, although LIF activated STAT3, the LIF-induced repression of the MCK transcriptional activity was not reversed by pretreatment with AG490, a specific Jak kinase inhibitor or transient transfection with DN-STAT3. Additionally, LIF exhibited its inhibitory effect on myogenesis only when cells were treated at earlier than 12 h after inducing differentiation. Taken together, these results suggest that LIF strongly inhibited early myogenic differentiation though activation of the ERK signaling pathway and its effect is irrespective of glycosylation.
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PMID:Leukemia inhibitory factor blocks early differentiation of skeletal muscle cells by activating ERK. 1584 32

In this study, we quantified the transcription of the interleukin-6 (IL-6) gene in individual fibres and the associated changes in calcineurin activity assessed at the cellular level during prolonged muscle contraction. Individual myofibres were isolated from plantaris and soleus muscles of rats at the end of an exhaustive running exercise test (n = 10), categorized according to their myosin heavy chain isoform content, and compared to those of resting rats (n = 10). Using real-time PCR analysis in individual fibres, a marked rise in IL-6 transcript levels occurred in type I and IIa fibres at the end of exercise (P < 0.05). Transcription of the gene encoding for the modulatory calcineurin-interacting protein-1 (MCIP-1), a sensitive indicator of calcineurin activity, also mainly increased in type I and IIa fibres (P < 0.05). Moreover, a slight increase in MCIP-1 mRNA levels was observed in type IIx (P < 0.05). Fibre types determined by immunohistochemistry were qualitatively examined for glycogen content using periodic acid-Shiff staining, and no direct relationship was found, at the cellular level, between glycogen content, fibre-type and IL-6 transcription. Our data clearly suggest that IL-6 gene transcription was mainly observed in early recruited myofibres and that contraction-induced IL-6 transcription could be associated with enhanced calcineurin activity.
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PMID:Fibre-type specificity of interleukin-6 gene transcription during muscle contraction in rat: association with calcineurin activity. 1590 11

Diabetic heart failure may be causally associated with alterations in cardiac energy metabolism and insulin resistance. Mice with heart-specific overexpression of peroxisome proliferator-activated receptor (PPAR)alpha showed a metabolic and cardiomyopathic phenotype similar to the diabetic heart, and we determined tissue-specific glucose metabolism and insulin action in vivo during hyperinsulinemic-euglycemic clamps in awake myosin heavy chain (MHC)-PPARalpha mice (12-14 weeks of age). Basal and insulin-stimulated glucose uptake in heart was significantly reduced in the MHC-PPARalpha mice, and cardiac insulin resistance was mostly attributed to defects in insulin-stimulated activities of insulin receptor substrate (IRS)-1-associated phosphatidylinositol (PI) 3-kinase, Akt, and tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3). Interestingly, MHC-PPARalpha mice developed hepatic insulin resistance associated with defects in insulin-mediated IRS-2-associated PI 3-kinase activity, increased hepatic triglyceride, and circulating interleukin-6 levels. To determine the underlying mechanism, insulin clamps were conducted in 8-week-old MHC-PPARalpha mice. Insulin-stimulated cardiac glucose uptake was similarly reduced in 8-week-old MHC-PPARalpha mice without changes in cardiac function and hepatic insulin action compared with the age-matched wild-type littermates. Overall, these findings indicate that increased activity of PPARalpha, as occurs in the diabetic heart, leads to cardiac insulin resistance associated with defects in insulin signaling and STAT3 activity, subsequently leading to reduced cardiac function. Additionally, age-associated hepatic insulin resistance develops in MHC-PPARalpha mice that may be due to altered cardiac metabolism, functions, and/or inflammatory cytokines.
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PMID:Cardiac-specific overexpression of peroxisome proliferator-activated receptor-alpha causes insulin resistance in heart and liver. 1612 38

To test the hypothesis that creatine supplementation would enhance the anabolic responses of muscle cell signaling and gene expression to exercise, we studied nine subjects who received either creatine or a placebo (maltodextrin) for 5 days in a double-blind fashion before undergoing muscle biopsies: at rest, immediately after exercise (10 x 10 repetitions of one-leg extension at 80% 1 repetition maximum), and 24 and 72 h later (all in the morning after fasting overnight). Creatine supplementation decreased the phosphorylation state of protein kinase B (PKB) on Thr308 at rest by 60% (P < 0.05) and that of eukaryotic initiation factor 4E-binding protein on Thr37/46 (4E-BP1) by 30% 24 h postexercise (P < 0.05). Creatine increased mRNA for collagen 1 (alpha(1)), glucose transporter-4 (GLUT-4), and myosin heavy chain I at rest by 250%, 45%, and 80%, respectively, and myosin heavy chain IIA (MHCIIA) mRNA immediately after exercise by 70% (all P < 0.05). Immediately after exercise, and independent of creatine, mRNA for muscle atrophy F-box (MAFbx), MHCIIA, peroxisome proliferator-activated receptor gamma coactivator-1alpha, and interleukin-6 were upregulated (60-350%; P < 0.05); the phosphorylation state of p38 both in the sarcoplasm and nucleus were increased (12- and 25-fold, respectively; both P < 0.05). Concurrently, the phosphorylation states of PKB (Thr308) and 4E-BP1 (Thr37/46) were decreased by 50% and 75%, respectively (P < 0.05). Twenty-four hours postexercise, MAFbx, myostatin, and GLUT-4 mRNA expression decreased below preexercise values (-35 to -50%; P < 0.05); calpain 1 mRNA increased 70% 72 h postexercise (P < 0.05) and at no other time. In conclusion, 5 days of creatine supplementation do not enhance anabolic signaling but increase the expression of certain targeted genes.
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PMID:Effects of resistance exercise with and without creatine supplementation on gene expression and cell signaling in human skeletal muscle. 1804 90

Skeletal myogenesis is potently regulated by the extracellular milieu of growth factors and cytokines. We observed that cardiotrophin-1 (CT-1), a member of the interleukin-6 (IL-6) family of cytokines, is a potent regulator of skeletal muscle differentiation. The normal up-regulation of myogenic marker genes, myosin heavy chain (MyHC), myogenic regulatory factors (MRFs), and myocyte enhancer factor 2s (MEF2s) were inhibited by CT-1 treatment. CT-1 also represses myogenin (MyoG) promoter activation. CT-1 activated two signaling pathways: signal transducer and activator of transcription 3 (STAT3), and mitogen-activated protein kinase kinase (MEK), a component of the extracellular signal-regulated MAPK (ERK) pathway. In view of the known connection between CT-1 and STAT3 activation, we surprisingly found that pharmacological blockade of STAT3 activity had no effect on the inhibition of myogenesis by CT-1 suggesting that STAT3 signaling is dispensable for myogenic repression. Conversely, MEK inhibition potently reversed the inhibition of myotube formation and attenuated the repression of MRF transcriptional activity mediated by CT-1. Taken together, these data indicate that CT-1 represses skeletal myogenesis through interference with MRF activity by activation of MEK/ERK signaling. In agreement with these in vitro observations, exogenous systemic expression of CT-1 mediated by adenoviral vector delivery increased the number of myonuclei in normal post-natal mouse skeletal muscle and also delayed skeletal muscle regeneration induced by cardiotoxin injection. The expression pattern of CT-1 in embryonic and post-natal skeletal muscle and in vivo effects of CT-1 on myogenesis implicate CT-1 in the maintenance of the undifferentiated state in muscle progenitor cells.
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PMID:Cardiotrophin-1 maintains the undifferentiated state in skeletal myoblasts. 1943 12


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