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 previous studies, we reported that prostaglandin F2alpha (PGF2alpha) stimulates phosphoinositide hydrolysis by phospholipase C and phosphatidylcholine hydrolysis by phospholipase D in osteoblast-like MC3T3-E1 cells. In the present study, we examined the effect of PGF2alpha on synthesis of interleukin-6 (IL-6) and the involvement of protein kinase C (PKC) activation in the IL-6 synthesis in these cells. PGF2alpha significantly stimulated IL-6 synthesis in a dose-dependent manner in the range between 10 nM and 10 microM. A PKC-activating phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), induced IL-6 synthesis. On the contrary, 4alpha-phorbol 12,13-didecanoate, a PKC-nonactivating phorbol ester, had no effect. The synthesis of IL-6 stimulated by a combination of PGF2alpha and TPA was not additive. Staurosporine, an inhibitor for protein kinases that suppressed the TPA-induced IL-6 synthesis, significantly inhibited the PGF2alpha-induced IL-6 synthesis. Calphostin C, a highly specific PKC inhibitor, also suppressed the PGF2alpha-stimulated synthesis of IL-6. The effect of PGF2alpha on IL-6 synthesis in PKC-downregulated cells was much weaker than that in intact cells. These results strongly suggest that PGF2alpha induces IL-6 synthesis via PKC activation in osteoblast-like cells.
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PMID:Prostaglandin F2alpha stimulates interleukin-6 synthesis via activation of PKC in osteoblast-like cells. 912 24

In previous studies, we have shown that prostaglandin F2alpha (PGF2alpha) stimulates interleukin-6 (IL-6) synthesis via activation of protein kinase C in osteoblast-like MC3T3-E1 cells, and that prostaglandin E1 (PGE1) induces the synthesis of IL-6 through protein kinase A activation. In the present study, we investigated the effect of vitamin D3 on IL-6 synthesis in MC3T3-E1 cells. 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3), an active form of vitamin D3, inhibited the IL-6 synthesis induced by PGF2alpha or PGE1. On the contrary, 24,25-dihydroxyvitamin D3, an inactive form of vitamin D3, had no effect. 1,25-(OH)2D3 did not affect the IL-6 synthesis stimulated by 12-O-tetradecanoyl-phorbol-13-acetate, an activator of protein kinase C. The IL-6 synthesis induced by cholera toxin or forskolin was significantly inhibited by 1,25-(OH)2D3. However, 1,25-(OH)2D3 had little effect on the IL-6 synthesis induced by dibutyryl cAMP. These results strongly suggest that 1,25-(OH)2D3, an active form of vitamin D3, inhibits IL-6 synthesis at both the protein kinase C pathway and the protein kinase A pathway in osteoblasts.
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PMID:Effect of vitamin D3 on interleukin-6 synthesis induced by prostaglandins in osteoblasts. 957 49

We previously reported that prostaglandin E1 (PGE1) induces the synthesis of interleukin-6 (IL-6) via cAMP production in osteoblast-like MC3T3-E1 cells, and that, on the other hand, prostaglandin F2alpha (PGF2alpha) stimulates IL-6 synthesis via activation of protein kinase C. In the present study, we examined the effect of retinoic acid on IL-6 synthesis induced by these two prostaglandins in MC3T3-E1 cells. Retinoic acid inhibited the IL-6 synthesis induced by PGF2alpha or PGE1 in a dose-dependent manner in the range between 0.1 and 10 nM. Retinoic acid also suppressed the IL-6 synthesis stimulated by 12-O-tetradecanoylphorbol-13-acetate, an activator of protein kinase C. The IL-6 synthesis induced by cholera toxin, forskolin or dibutyryl cAMP was inhibited by retinoic acid. However, retinoic acid had little effect on the IL-6 synthesis induced by interleukin-1. These results indicate that retinoic acid inhibits IL-6 synthesis induced by prostaglandins in osteoblasts as follows: the inhibitory effect on the PGE1-induced IL-6 synthesis is exerted at a point downstream from cAMP, and the inhibitory effect on the PGF2alpha-induced IL-6 synthesis is exerted at a point downstream from protein kinase C.
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PMID:Retinoic acid suppresses interleukin-6 synthesis induced by prostaglandins in osteoblasts. 961 Aug 45

Prostaglandin F2alpha (PGF2alpha) significantly induced p42/p44 mitogen-activated protein (MAP) kinase activity in osteoblast-like MC3T3-E1 cells. PD98059, a selective inhibitor of MAP kinase kinase, inhibited PGF2alpha-induced interleukin-6 (IL-6) synthesis as well as PGF2alpha-induced p42/p44 MAP kinase activation. PD98059 suppressed the IL-6 synthesis induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), a protein kinase C (PKC) activator, or NaF, an activator of heterotrimeric GTP-binding protein, as well as the p42/p44 MAP kinase activation by TPA or NaF. Calphostin C, a highly potent and specific inhibitor of PKC, inhibited the PGF2alpha-induced p42/p44 MAP kinase activity. These results strongly suggest that PKC-dependent p42/p44 MAP kinase activatioin is involved in PGF2alpha-induced IL-6 synthesis in osteoblasts.
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PMID:p42/p44 mitogen-activated protein kinase activation is involved in prostaglandin F2alpha-induced interleukin-6 synthesis in osteoblasts. 1037 4

We have developed methods for the isolation, cultivation, and investigation of human uveal melanocytes (UM). Uveal melanocytes grow well and produce melanin in vitro in the presence of basic fibroblast growth factor (bFGF), cyclic adenosine monophosphate-elevating agents, and serum. Cultured UM respond to various factors. Certain growth factors (bFGF and hepatocyte growth factor, etc.), endothelin, adrenergic beta2-receptor agonists, and some prostaglandins (EP2-receptor agonists and certain TP-receptor agonists) stimulate, while transforming growth factor-beta2, interleukin-6, and cholinergic agonists inhibit melanogenesis and/or growth of UM in vitro. Alpha-melanocyte-stimulating hormone, adrenocorticotropic hormone, various sex hormones, and prostaglandin F2alpha showed no effect on the growth and melanogenesis of cultured UM. The stability of UM in vivo may be controlled by these factors. Disturbance of this balance may lead to certain rare pathologic pigmentary changes of the iris. UM are relatively stable in vivo; they usually do not respond (proliferate or show dynamic changes in melanogenesis) to various environmental factors. The differences of the in vivo behavior between uveal and epidermal melanocytes may be determined by both cellular factors and environmental factors.
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PMID:Regulation of growth and melanogenesis of uveal melanocytes. 1104 62

There has been no investigation to determine if the widely used over-the-counter, water-soluble antioxidants vitamin C and N-acetyl-cysteine (NAC) could act as pro-oxidants in humans during inflammatory conditions. We induced an acute-phase inflammatory response by an eccentric arm muscle injury. The inflammation was characterized by edema, swelling, pain, and increases in plasma inflammatory indicators, myeloperoxidase and interleukin-6. Immediately following the injury, subjects consumed a placebo or vitamin C (12.5 mg/kg body weight) and NAC (10 mg/kg body weight) for 7 d. The resulting muscle injury caused increased levels of serum bleomycin-detectable iron and the amount of iron was higher in the vitamin C and NAC group. The concentrations of lactate dehydrogenase (LDH), creatine kinase (CK), and myoglobin were significantly elevated 2, 3, and 4 d postinjury and returned to baseline levels by day 7. In addition, LDH and CK activities were elevated to a greater extent in the vitamin C and NAC group. Levels of markers for oxidative stress (lipid hydroperoxides and 8-iso prostaglandin F2alpha; 8-Iso-PGF2alpha) and antioxidant enzyme activities were also elevated post-injury. The subjects receiving vitamin C and NAC had higher levels of lipid hydroperoxides and 8-Iso-PGF2alpha 2 d after the exercise. This acute human inflammatory model strongly suggests that vitamin C and NAC supplementation immediately post-injury, transiently increases tissue damage and oxidative stress.
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PMID:Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise. 1155 12

We previously reported that prostaglandin F2alpha (PGF2alpha) induces phosphoinositide hydrolysis by phospholipase C and phosphatidylcholine hydrolysis by phospholipase D through heterotrimeric GTP-binding protein, resulting in the activation of protein kinase C (PKC) in osteoblast-like MC3T3-E1 cells and that PGF2alpha stimulates the synthesis of interleukin-6 (IL-6) via PKC-dependent p44/p42 mitogen-activated protein (MAP) kinase activation. In the present study, we investigated whether zinc affects the PGF2alpha-induced IL-6 synthesis in these cells. Zinc complex of l-carnosine (l-CAZ) dose-dependently suppressed the PGF2alpha-stimulated IL-6 synthesis. In addition, zinc alone reduced the IL-6 synthesis. L-CAZ suppressed the PGF2alpha-induced p44/p42 MAP kinase phosphorylation. However, the p44/p42 MAP kinase phosphorylation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), a direct activator of PKC, or NaF, a direct activator of GTP-binding protein, was not affected by l-CAZ. l-CAZ reduced the PGF2alpha-stimulated formation of inositol phosphates and choline. However, l-CAZ did not affect the formation of inositol phosphates or choline induced by NaF. These results strongly suggest that zinc reduces PGF2alpha-induced IL-6 synthesis via suppression of phosphoinositide-hydrolyzing phospholipase C and phosphatidylcholine-hydrolyzing phospholipase D in osteoblasts.
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PMID:Zinc suppresses IL-6 synthesis by prostaglandin F2alpha in osteoblasts: inhibition of phospholipase C and phospholipase D. 1196 2

Low-dose aspirin (acetylsalicylic acid) is used as prophylaxis against cardiovascular diseases. The effect of aspirin on inflammation and oxidative stress, processes known to be involved in cardiovascular diseases, are not fully known. The cyclooxygenase(COX)-mediated inflammatory indicator prostaglandin F2alpha (PGF2alpha) (15-keto-dihydro-PGF2alpha), cytokine-mediated inflammatory indicators (interleukin-6, high-sensitivity C-reactive protein, serum amyloid A protein), and oxidative stress indicators (8-iso-PGF2alpha, tocopherols) were quantified in men with daily 75 mg of aspirin (n=175) and control men (n=464), all of age 77, in a cross-sectional study. Men treated with aspirin had decreased levels of urinary 15-keto-dihydro-PGF2alpha than controls (P<0.01), independent of possible cardiovascular risk factors. Aspirin-treated men had increased levels of alpha-tocopherol than controls (P<0.05). This is the first study to indicate that low-dose aspirin treatment is associated with decreased levels of PGF2alpha. This observation suggests a possible COX-mediated anti-inflammatory effect of low-dose aspirin, which should be further confirmed by intervention studies.
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PMID:Cyclooxygenase-mediated prostaglandin F2alpha is decreased in an elderly population treated with low-dose aspirin. 1576 33

Low concentrations of selenium (Se) predict mortality and cardiovascular diseases in some populations. The effect of Se on in vivo indicators of oxidative stress and inflammation, two important features of atherosclerosis, in human populations is largely unexplored. This study investigated the longitudinal association between serum selenium (s-Se) and a golden standard indicator of oxidative stress in vivo (8-iso-prostaglandin F2alpha, a major F2-isoprostane), an indicator of cyclooxygenase (COX)-mediated inflammation (prostaglandin F2alpha), high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6) and serum amyloid A protein (SAA) in a follow-up study of 27 years. The s-Se was measured in 615 Swedish men at 50 years of age in a health investigation. The status of oxidative stress and inflammation was evaluated in a re-investigation 27 years later by quantification of urinary 8-iso-PGF2alpha and 15-keto-dihydro-PGF2alpha (a major metabolite of PGF2alpha) and serum hsCRP, SAA and IL-6. Men in the highest quartile of s-Se at age 50 had decreased levels of 8-iso-PGF2alpha compared to all lower quartiles and decreased levels of PGF2alpha compared to all lower quartiles at follow-up. These associations were independent of BMI, diabetes, hyperlipidemia, hypertension, smoking, alpha-tocopherol and beta-carotene at baseline. The s-Se was not associated with hsCRP, SAA or IL-6 at follow-up. In conclusion, high concentrations of s-Se predict reduced levels of oxidative stress and subclinical COX-mediated (but not cytokine-mediated) inflammation in a male population. The associations between Se, oxidative stress and inflammation, respectively, might be related to the proposed cardiovascular protective property of Se.
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PMID:Serum selenium predicts levels of F2-isoprostanes and prostaglandin F2alpha in a 27 year follow-up study of Swedish men. 1603 56

Leukemia inhibitory factor (LIF) and oncostatin M (OSM) induce DNA synthesis in Swiss 3T3 cells through common signaling mechanism(s), whereas other related cytokines such as interleukin-6 and ciliary neurotrophic factor do not cause this response. Induction of DNA replication by LIF or prostaglandin F2alpha (PGF2alpha) occurs, in part, through different signaling events. LIF and OSM specifically trigger STAT1 cytoplasmic to nuclear translocation, whereas PGF2alpha fails to do so. However, LIF and PGF2alpha can trigger increases in ERK1/2 activity, which are required for their mitogenic responses because U0126, a MEK1/2 inhibitor, prevents both ERK1/2 activation and induction of DNA synthesis by LIF or PGF2alpha treatment. PGF2alpha induces cyclin D expression and full phosphorylation of retinoblastoma protein. In contrast, LIF fails to promote increases in cyclin D mRNA/protein levels; consequently, LIF induces DNA synthesis without promoting full phosphorylation of retinoblastoma protein (Rb). However, both LIF and PGF2alpha increase cyclin E expression. Furthermore, LIF mitogenic action does not involve protein kinase C (PKC) activation, because a PKC inhibitor does not block this effect. In contrast, PKC activity is required for PGF2alpha mitogenic action. More importantly, the synergistic effect between LIF and PGF2alpha to promote S phase entry is independent of PKC activation. These results show fundamental differences between LIF- and PGF2alpha-dependent mechanism(s) that induce cellular entry into S phase. These findings are critical in understanding how LIF and other related cytokine-regulated events participate in normal cell cycle control and may also provide clues to unravel crucial processes underlying cancerous cell division.
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PMID:Leukemia inhibitory factor induces DNA synthesis in Swiss mouse 3T3 cells independently of cyclin D1 expression through a mechanism involving MEK/ERK1/2 activation. 1629 39


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