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)

It has been demonstrated that calcitonin-binding sites are present in a variety of tissue types, including in the pituitary gland. Interleukin-6 (IL-6) is also produced in the pituitary and it regulates the secretion of various hormones. In this study, we examined the expression of the calcitonin receptor and the mechanism of IL-6 production induced by calcitonin in the pituitary folliculo-stellate cell line (TtT/GF). The mRNA of calcitonin receptor subtype C1a, but not that of C1b, was detected by RT-PCR in TtT/GF cells and in the normal mouse pituitary. Calcitonin increased cAMP accumulation and IL-6 production in a concentration-dependent manner in TtT/GF cells. As calcitonin activates the PKA and PKC pathways, we investigated the contributions of PKA and PKC to IL-6 production. IL-6 production was only slightly increased by either 8-bromo-cAMP (1 mM) or phorbol 12-myristate 13-acetate (100 nM) alone. However, IL-6 was synergistically induced in the presence of both 8-bromo-cAMP (1 mM) and phorbol 12myristate 13-acetate (100 nM). Furthermore, calcitonin-induced IL-6 production was completely suppressed by H-89 (PKA inhibitor) or GF109203X (PKC inhibitor), indicating that the activation of both PKA and PKC is necessary for calcitonin-induced IL-6 production. On the other hand, pertussis toxin (G(i)/G(o) signaling inhibitor) treatment achieved an approximately 9-fold increase in calcitonin-induced IL-6 production. These results show that calcitonin-stimulated IL-6 production is mediated via both PKA- and PKC-signaling pathways, whereas calcitonin also suppresses IL-6 production by activating G(i)/G(o) proteins in folliculo-stellate cells.
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PMID:Calcitonin induces IL-6 production via both PKA and PKC pathways in the pituitary folliculo-stellate cell line. 1145 4

Osteoporosis is a disease affecting mainly women but also an increasing number of men. The destruction of the bone microarchitecture and the reduction of bone mass lead to increased fragility and pathologic bone fractures. Family studies and twin studies have shown that peak bone mass, mechanical strength, and physiological bone turnover are subject to genetic control. Vitamin D receptor polymorphisms were one of the first genetic factors suggested to influence bone phenotype, although their impact on bone metabolism was initially overestimated. Meanwhile, polymorphisms in numerous other genes such as collagen I alpha 1, estrogen receptor, transforming growth factor beta (TGF-beta), interleukin-1, interleukin-6, calcitonin, parathyroid hormone, and apolipoprotein E have been found to be associated with bone mineral density. In the interpretation of genetic findings, genetic differences between different ethnic groups, environmental factors such as calcium intake, vitamin D status, hormonal status, body size, and total body bone mineral density have to be considered. Understanding the molecular physiology of the genes described in this article and all genes influencing bone metabolism identified in the future will enable us to identify persons at risk for osteoporosis and to develop more specific therapies.
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PMID:[Genetics of osteoporosis]. 1151 78

We found that substance P (SP) and calcitonin gene-related peptide (CGRP) (0.3-1 microM) increased, in a concentration-dependent manner, the basal secretion of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF alpha) from cultured lymphocyte-enriched mononuclear cells isolated from human peripheral blood. SP and CGRP (0.1 microM) synergistically increased basal TNF alpha secretion. Dynorphin A((1-17)) (0.1-1 microM) did not modify basal cytokine secretion. Lipopolysaccharide (10 ng/ml)-induced cytokine secretion and [(3)H]thymidine uptake were not altered by any neuropeptide (at 0.1 microM). Thus, SP and CGRP stimulate the production of pro-inflammatory cytokines from lymphocytes only at high concentrations, similar to those reached during tissue damage.
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PMID:Substance P and calcitonin gene-related peptide increase IL-1 beta, IL-6 and TNF alpha secretion from human peripheral blood mononuclear cells. 1179 59

Interleukin-6 (IL-6) contributes to increased pain and hyperalgesia in inflamed tissue. We have investigated the effects of IL-6, alone or in combination with its soluble receptor (sIL-6R), on the sensitivity of nociceptors to noxious heat, using dermal microdialysis. Plasmapheresis membranes were inserted into the abdominal skin of adult male Wistar rats (n=46) and perfused with modified Ringer solution. After three control samples (20 min each), the skin area above the membrane was heated to 48 degrees C for 20 min. The stimulation was followed by two washout samples. The calcitonin gene-related peptide (CGRP) content of the dialysate was measured with an enzyme immunoassay. Heat stimulation provoked a significant CGRP increase in the dialysate. Intradermal application of IL-6 (200 ng ml-1) did not significantly alter heat-induced CGRP release. However, a significant sensitisation of the heat-induced CGRP release was observed when sIL-6R (25 ng ml-1) was applied, either alone or in combination with IL-6. Neutralisation of endogenous IL-6 with a sheep anti-rat IL-6 serum did not alter heat-induced CGRP release, but abolished the sIL-6R-mediated sensitising effect. We show that IL-6 in combination with its soluble receptor can sensitise nociceptors to heat and provide evidence for the constitutive expression of the signalling molecule gp130, but not of the IL-6-membrane-bound (specific) receptor, in nociceptors.
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PMID:Interleukin-6 in combination with its soluble IL-6 receptor sensitises rat skin nociceptors to heat, in vivo. 1193 61

Oncostatin M belongs to the interleukin-6 family of cytokines and acts as a multifunctional cytokine during murine embryogenesis and in inflammatory reactions. Although it has been demonstrated that oncostatin M has biological activities on many types of cells, including hepatocytes, dermal fibroblasts and endothelial cells, the roles of oncostatin M in the murine peripheral nervous system remain unclear. Here, we investigated the expression of specific beta-subunit of oncostatin M receptor in the dorsal root ganglia of adult mice. In the adult dorsal root ganglia, beta-subunit of oncostatin M receptor was exclusively expressed in small-sized neurons. Approximately 13% of total dorsal root ganglia neurons in mice contained beta-subunit of oncostatin M receptor. The double-immunofluorescence method revealed that approximately 28% of beta-subunit of oncostatin M receptor-positive neurons contained TrkA immunoreactivity, 63% expressed Ret immunoreactivity and 58% bound isolectin B4. No neuropeptides, including substance P and calcitonin gene-related peptide, were contained in the neurons. In addition, all beta-subunit of oncostatin M receptor-positive neurons expressed both vanilloid receptor 1 and P2X3 purinergic receptor. These neurons projected to the inner portion of lamina II in the dorsal horn of spinal cord and the dermis of skin. Seven days after sciatic nerve axotomy, the expression of beta-subunit of oncostatin M receptor was down-regulated in the lumbar dorsal root ganglia of the injured side. Our study demonstrated that beta-subunit of oncostatin M receptor was expressed in both cell bodies and processes of nonpeptidergic nociceptive neurons in adult mice, suggesting that oncostatin M may affect the nociceptive function of the neurons through the modulation of vanilloid receptor 1 and P2X3 expression.
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PMID:Expression of oncostatin M receptor beta in a specific subset of nociceptive sensory neurons. 1281 62

The sepsis is a bacterial invasion of the organism producing many manifestations which are able to amplify themselves. In the United States of America there are 100,000 death per year and the incidence is among 300,000-500,000 cases. The major surgery in the elder (especially if it is in emergency) has a great percental of risk because the preoperative study isn't often complete. Fever, agitation, panting, bullation, abdominal splinting, enteroplegia, are signals of evolving inflammatory situation. Moreover there are disorders of biochemical values: leukocytosis, thrombocytopenia, increased levels of VES, PCR, amylase and biliribinaemia. The more common radiological examinations are the straight radiography of abdomen and horax, abdomen ultrasonography, CT or MRI. In the last years pro-calcitonin, interleukin-6 , C-reactive protein, and nitric oxide from endothelial and muscularis cells have been evaluated as prognostic factors in the septic shock.
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PMID:[Septic shock: surgical and medical problems in the elderly]. 1467 79

The effects of cystatin C and other cysteine proteinase inhibitors on osteoclast formation and differentiation have been investigated. Cystatin C decreased osteoclast formation stimulated by parathyroid hormone (PTH), 1,25(OH)2-vitamin D3 or interleukin-6 (IL-6) (in the presence of its soluble receptor) as assessed by the number of tartrate-resistant acid phosphatase (TRAP+) multinucleated cells in mouse bone marrow cultures. The inhibitory effect was associated with decreased mRNA expression for the calcitonin receptor as well as decreased number of specific binding sites for 125I-calcitonin, and without any effect on the mRNA expression of receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL). Similarly, the cysteine proteinase inhibitors leupeptin, E-64 and benzyloxycarbonyl-Phe-Ala-diazomethane (Z-FA-CHN2) decreased PTH-stimulated formation of TRAP+ multinucleated cells and binding of 125I-calcitonin. A peptidyl derivative synthesized to mimic part of the proteinase-binding site of cystatin C (benzyloxycarbonyl-Arg-Leu-Val-Gly-diazomethane, or Z-RLVG-CHN2) also decreased PTH-stimulated osteoclast formation. In a 9-day culture, addition of cystatin C during the last 5 days was sufficient to cause substantial inhibition of osteoclast formation. Cystatin C-induced decrease of osteoclast formation was associated with enhanced number of F4/80-positive macrophages and increased mRNA expression of the macrophage receptor c-fms in the bone marrow culture. Osteoclast formation in mouse bone marrow cultures as well as in mouse spleen cell cultures, stimulated by macrophage colony-stimulating factor (M-CSF) and RANKL was also decreased by different cysteine proteinase inhibitors. In addition, cystatin C inhibited M-CSF/RANKL induction of calcitonin receptor mRNA in spleen cell cultures. The inhibitory effect by cystatin C in spleen cells was associated with decreased mRNA expression of RANK and the transcription factor NFAT2. It is concluded that cysteine proteinase inhibitors decrease formation of osteoclasts by interfering at a late stage of pre-osteoclast differentiation.
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PMID:Osteoclastogenesis is decreased by cysteine proteinase inhibitors. 1500 89

The expression pattern of proinflammatory cytokines, neuronal nitric oxide synthase (nNOS), substance P (SP) and calcitonin gene related peptide (CGRP) in the spinal cord and the bladder in response to permanent middle cerebral artery occlusion (MCAO) was investigated. In this connection, the gene expression of tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1beta) and interleukin-6 in the lumbosacral spinal cord and the bladder as determined by real-time polymerase chain reaction was upregulated. In the spinal cord, the immunoreactivity of TNF-alpha and IL-1beta was mainly localized in the ventral horn motoneurons contralateral to MCAO. In the bladder, TNF-alpha was mainly expressed in the inflammatory cells. The expression of nNOS immunoreactivity as well as nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) staining in the spinal cord and bladder was also markedly increased in response to MCAO. Furthermore, the temporal and spatial expression of nNOS paralleled that of TNF-alpha and IL-1beta in the spinal cord. On the other hand, there was no noticeable change in gene expression and immunoreactivity of SP and CGRP. The present results have shown that cytokines and nNOS expression are elevated in areas far removed from the primary site of ischemic infarct, namely, the lumbosacral spinal cord and bladder. This together with some neuronal deaths maybe linked to the dysfunction of the latter in a clinical stroke. On the other hand, the apparent lack of SP and CGRP changes following MCAO suggests that the two neurotransmitters are not directly involved.
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PMID:Permanent occlusion of the middle cerebral artery upregulates expression of cytokines and neuronal nitric oxide synthase in the spinal cord and urinary bladder in the adult rat. 1512 Aug 43

We report the program of gene expression during osteoclast formation from RAW264.7 cell precursors in response to RANK-ligand (RANK-L) using a combination of quantitative real time PCR and Affymetrix gene chip assays. We found that genes obligatory to osteoclast formation and function, namely tartrate-resistant acid phosphatase, cathepsin K, beta3 integrin, and calcitonin receptors, were up-regulated by RANK-L markedly by up to approximately 2000-fold. In contrast, we found a cluster of genes that were significantly down-regulated: these included interleukin-18, insulin-like growth factor-1, interleukin-6 receptor, and cathepsins B, C, and L. These results from real time PCR were broadly concordant with those obtained from Affymetrix. We also explored the expression of the transcription factors of the NFAT and NFkappaB family at days 3 and 5 of culture. Whereas NFATc1 expression was increased significantly at days 3 and 5 following RANK-L exposure, there were no significant increases in the expression of NFkappaB subunits, namely p65, p50, c-Rel, IkappaBalpha, and IkappaBbeta. There were also no significant differences in transcription modulator expression between days 3 and 5, except for c-Rel and NFATc4, which were both decreased significantly at day 5. The studies suggest RANK-L regulates the expression only of NFATc1, while it signals through both NFATc1 and NFkappaB.
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PMID:RANK-L induces the expression of NFATc1, but not of NFkappaB subunits during osteoclast formation. 1556 62

The pro-inflammatory cytokine interleukin-6 (IL-6) together with its soluble receptor (sIL-6R) induces and maintains thermal hyperalgesia. It facilitates the heat-induced release of calcitonin gene-related peptide from rat cutaneous nociceptors in vivo and in vitro. Here we report that exposure of nociceptive neurons to the IL-6-sIL-6R complex or the gp130-stimulating designer IL-6-sIL-6R fusion protein Hyper-IL-6 (HIL-6) resulted in a potentiation of heat-activated inward currents (I(heat)) and a shift of activation thresholds towards lower temperatures without affecting intracellular calcium levels. The Janus tyrosine kinase inhibitor AG490, the selective protein kinase C (PKC) inhibitor, bisindolylmaleimide 1 (BIM1), as well as rottlerin, a selective blocker of the PKCdelta isoform, but not the cyclooxygenase inhibitor indomethacin, effectively reduced the effect. Reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization revealed expression of mRNA for the signal-transducing beta subunit of the receptor gp130 in neuronal somata, rather than satellite cells in rat dorsal root ganglia. Together, the results suggest that IL-6-sIL-6R acts directly on sensory neurons. It increases their susceptibility to noxious heat via the gp130/Jak/PKCdelta signalling pathway.
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PMID:Fast modulation of heat-activated ionic current by proinflammatory interleukin 6 in rat sensory neurons. 1581 18


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