Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present report, we show that progressive growth of the immunogenic C57BL/6J sarcoma, MCA/76-9, was accompanied by an increase in serum interleukin-6 (IL-6) activity. The possible pathways leading to the induction of IL-6 release by the tumor cells are described. It was shown that macrophage products IL-1 alpha, IL-1 beta, and to a lesser extent, TNF alpha, induced the tumor cells in vitro to transcribe the IL-6 gene and release the gene product. IL-1 induced significantly more IL-6 mRNA and bioactivity than TNF alpha, although both cytokines induced a cumulative increase of bioactivity in the supernates over a period of 24 h. The tumor cells were shown to express receptors for IL-1 alpha, which could be blocked with anti-IL-1 receptor antibody. Given the previous reports that tumor-associated macrophages expressed both IL-1 alpha/beta and TNF alpha, the data suggest, first, that the mutual interaction of tumor cells and macrophages in situ may contribute to the observed increase in circulating IL-6 activity, and second, that the release of IL-6 in vivo may serve to regulate both anti-tumor immune responses and suppressor mechanisms.
 ...
PMID:Tumor cell IL-6 gene expression is regulated by IL-1 alpha/beta and TNF alpha: proposed feedback mechanisms induced by the interaction of tumor cells and macrophages. 140 92

The kinetic profile of cytokine gene expression in normal human peripheral mononuclear cells (MNC) activated by an anti-CD3 monoclonal antibody was studied. The presence or absence of 10 different cytokine mRNA were measured in a polymerase chain reaction (PCR) assisted mRNA amplification assay. After 2 h of stimulation the mRNA for interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2), interleukin-3 (IL-3), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were detectable and remained present during the whole time period studied (22 h). Interleukin-6 (IL-6) and granulocyte macrophage colony stimulating factor (GM-CSF) were detected after 4 h, while interleukin-10 (IL-10) mRNA did not appear until after 7 h; they all remained expressed at 22 h. A transient expression of interleukin-4 (IL-4) mRNA was observed between 4 and 7 h of stimulation. No gene expression of granulocyte colony stimulating factor (G-CSF) was detected at any time. These results show that anti-CD3 stimulation of MNC leads to a rapid sequential induction of different cytokine mRNA, some with a very transient expression.
 ...
PMID:OKT3-induced cytokine mRNA expression in human peripheral blood mononuclear cells measured by polymerase chain reaction. 143 86

Recent evidence suggests that diverse endometrial functions may be regulated by cytokines. In this report, the presence of protein and mRNA of cytokines were studied in human endometrium throughout the menstrual cycle. The presence of the interleukin-1 (IL-1) alpha, interleukin-1 (IL-1) beta, interleukin receptor antagonist (IRAP), interleukin-6 (IL-6) and transforming growth factor (TGF)-alpha proteins were demonstrated by immunohistochemical staining. The IL-1 alpha and TGF-alpha proteins were strongly expressed and IL-1 beta protein was weakly expressed in all the cells in the stroma as well as epithelial cells. IRAP was markedly expressed in the cells with morphological features of macrophages scattered in the stroma, and the expression of IL-6 protein was predominant in the endometrial epithelium. Diffuse cytoplasmic expression of IL-1 alpha in endometrial epithelium during the proliferative phase contrasted markedly with its enhanced luminal expression during the secretory phase of the menstrual cycle. In addition, the presence of the mRNA of these cytokines in endometrium was established throughout the entire menstrual cycle by reverse transcription-polymerase chain reaction (RT-PCR). Abundant expression of cytokines in human endometrium emphasizes the significant roles that cytokines play in cell-cell interactions and in regulating endometrial functions.
 ...
PMID:Cytokine expression in human endometrium throughout the menstrual cycle. 147

We established a new cell line (TC-1) from primary site of a renal cell carcinoma (RCC) patient. Its doubling time in tissue culture was 20 hours at 45th passage and mycoplasma contamination test was negative. The karyotypic analysis demonstrated a human karyotype with a modal number of 70. A consistent chromosomal abnormality was noted such as No. 4 monosomy, No. 7 trisomy and a loss of Y chromosome. Electron microscopic examination showed a brush border, vacuoles and abundant glycogen granules in the cytoplasm, which was compatible with RCC cells. This cell line was transplantable to nude mice and the grown tumor closely resembled the original tumor, i.e. clear cell type and hypervascularity. High titer of interleukin-6 (IL-6) was detected in the supernatant of TC-1 cell culture (approximately 5 ng/ml) as well as in sera of nude mice bearing this tumor (260 pg/ml). Exogenous IL-6 did not enhance the TC-1 cell proliferation as determined by cell count. Flow cytometric analysis could not demonstrate the existence of IL-6 receptor on the cell surface. These results suggested the produced IL-6 did not act as an autocrine growth factor in the cell line. Additional IL-1 alpha to the culture medium induced 3-4 times higher concentration of IL-6 in the culture supernatant compared with that of non-stimulating cells, while exogenous TNF alpha did not stimulate IL-6 production.
 ...
PMID:[Establishment of a new human renal cancer cell line (TC-1) and its productivity of interleukin-6 (IL-6)]. 147 60

Uterine stromal (USC) and uterine epithelial (UEC) cells were isolated from immature and mature mice to determine their ability to secrete interleukin-6 (IL-6) in response to ovarian steroids, IL-1 alpha, and soluble products produced by the heterologous cell type. In addition, the effect of IL-6 on embryo attachment and outgrowth in vitro was determined. UEC cultured on nitrocellulose filter inserts in a polarized manner secreted IL-6 with a 2.5- to 5-fold apical vs. basal preference, as determined by a B9 hybridoma cell proliferation assay and enzyme-linked immunosorbent assay. The hormonal status of animals at the time uteri were removed did not influence subsequent secretion of IL-6, as UEC isolated from immature, diestrous, and estrous stage mice exhibited both a similar amount and had a similar apical preference for secretion of IL-6. The addition of 17 beta-estradiol (E) to UEC cultures markedly inhibited total IL-6 secretion, but did not affect vectorial secretion. The inhibitory effect of E on IL-6 secretion by UEC was consistent with an apparent decrease in IL-6 transcript observed by a reverse transcriptase polymerase chain reaction assay. Other transcripts detected by this assay in UEC included IL-1 alpha, but not IL-1 beta or tumor necrosis factor-alpha. Secretion of IL-6 by UEC was not stimulated by IL-1 alpha, conditioned medium from USC, or coculture with USC. USC secreted IL-6, and while this also was inhibited by E, progesterone was more effective in this regard at physiological concentrations. In addition, there was a synergistic effect of E plus progesterone on inhibition of IL-6 secretion by USC. Secretion of IL-6 by USC was stimulated by IL-1 alpha, and coculture studies demonstrated the ability of UEC to stimulate a several-fold increase in IL-6 secretion by USC. The cytokine transcripts detected in USC cultures included IL-6 and IL-1 alpha, but not IL-1 beta. Transcripts for tumor necrosis factor-alpha were present in USC only after culture with IL-1 alpha. IL-6 added to blastocysts on laminin-coated tissue culture wells resulted in a transient inhibition of the rate of blastocyst attachment and, to a greater extent, an inhibition of the rate of embryo outgrowth. In addition, IL-6 inhibited the size of embryo outgrowths at 24 and 48 h of culture.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Secretion and hormonal regulation of interleukin-6 production by mouse uterine stromal and polarized epithelial cells cultured in vitro. 150 48

We investigated the expression and biological activity of interleukin-6 (IL-6) by human fibroblasts cultured as monolayers and within three-dimensional type I collagen lattices. In the course of contracting the gel to a dense tissue-like structure, the cells upregulated their levels of IL-6 mRNA as well as IL-6 biological activity. While there was little mRNA and protein activity (6,500 U/ml) in monolayer cultures, fibroblasts in the 3D system showed a 13-fold increase in IL-6 mRNA on day 3. IL-6 protein was increased 6-fold (38,000 U/ml) on day 4. Stimulation of fibroblast cultures with IL-1 alpha resulted in enhanced IL-6 production in both systems, but the fibroblasts embedded into the 3D network continued to exhibit higher levels.
 ...
PMID:Interleukin-6 expression by fibroblasts grown in three-dimensional gel cultures. 154 51

Recently, the mitogenic effects of the Mycoplasma arthritidis supernatant, MAS, and the induction of interferon-gamma (IFN-gamma) and interleukin-6 (IL-6) by MAS have been described. In the present series of experiments we investigated human peripheral blood mononuclear cells (PBM) and human spleen cells with respect to their production of these and other cytokines. In human spleen cell cultures and PBM, MAS induced the synthesis of interleukin-1 alpha (IL-1 alpha) and IL-1 beta. Both interleukins were secreted faster and in higher amounts by PBM. IL-6 was also induced by MAS in PBM and human spleen cells. The amounts of IL-6 measured by ELISA were higher in PBM, whereas the biological activity of IL-6 was higher in spleen cell cultures. T-cell products such as IL-2, IL-4, and IFN-gamma were also induced by MAS in PBM and spleen cells. The kinetics of IFN-gamma and IL-4 induction were negatively correlated. In PBM we found low levels of IL-4 and high IFN-gamma induction, whereas in spleen cells high titers of IL-4 and low IFN-gamma titers were observed. Collectively, our results indicate that MAS induces different networks of cytokine interactions depending on the organ from which the cells are derived.
 ...
PMID:Induction of cytokines in human peripheral blood and spleen cells by the Mycoplasma arthritidis-derived superantigen. 158 16

The cytokine interleukin-6 (IL-6) is the major phosphoprotein secreted by human fibroblasts induced with interleukin-1 alpha (IL-1 alpha). We have determined that Ser54 is the predominant site of phosphorylation on the fibroblast-derived IL-6 polypeptide; the amino acid motif surrounding this site is reminiscent of the target site for the Golgi-associated protein (casein) kinase. It has been shown earlier that the IL-6 polypeptide follows the classical secretory pathway where N-linked glycosylation is detectable within the first 15 minutes of labeling with [35S]-methionine and O-linked glycosylation occurs between 15-30 minutes after the start of polypeptide synthesis. Pulse-chase experiments using [32P]-orthophosphate or [35S]-methionine as tracers indicated that phosphorylation of IL-6 occurred prior to its O-glycosylation suggesting that the de novo synthesized IL-6 polypeptide is rapidly, perhaps even cotranslationally, phosphorylated at an intravesicular site (in the endoplasmic reticulum and/or Golgi). When IL-1 alpha-induced fibroblasts were exposed to cycloheximide there was enhancement of the net de novo synthesis and secretion of IL-6 as followed by [35S]-methionine labeling ("superinduction") but the secreted cytokine was no longer phosphorylated as monitored by [32P] labeling. Thus, phosphorylation of the IL-6 polypeptide is not an obligatory requirement for secretion of this cytokine. Furthermore, IL-6 phosphorylation is inhibited by cycloheximide through a mechanism different from the drug's effects on polypeptide synthesis per se.
 ...
PMID:Phosphorylation of interleukin-6 at serine54: an early event in the secretory pathway in human fibroblasts. 161 Mar 48

We have been investigating the production of cytokines in ocular tissues. In this paper, we demonstrated the in vitro production of interleukin-6 (IL-6) by human corneal epithelial, stromal and endothelial cells using enzyme-linked immunosorbent assay (ELISA). In culture supernatant of the stromal cells, the production of immunoreactive IL-6 was induced, depending upon the doses of lipopolysaccharide (LPS) or IL-1 alpha added into the culture. Detectable IL-6 activity in the supernatant of the stromal cells was found 2 hours after addition of IL-1 alpha and the activity increased to a peak level at 48 hours. On the other hand, in the supernatant of the endothelial cells, IL-6 activity was found even in unstimulated-culture, and induced further by LPS stimulation. The molecular weights (MWs) of the IL-6 produced by the epithelial, stromal and endothelial cells were calculated by gel filtration as about 30 kDa. From Western blotting analysis, the MW of IL-6 produced by the stromal cells was also determined to be 30 kDa.
 ...
PMID:[Human corneal epithelial, stromal and endothelial cells produce interleukin-6]. 162 70

The production of tumor necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) by stimulated peripheral blood monocytes/macrophages (PBM) was assessed in patients with multiple sclerosis (MS), other neurological diseases (OND) or normal controls (NC) using enzyme-linked immunosorbent assay (ELISA). PBM obtained from acute phase of MS produced significantly higher amount of all these cytokines than those from chronic stable MS, OND or NC (TNF alpha, IL-1 alpha, IL-6: p less than 0.01, IL-1 beta: p less than 0.05). Methylprednisolone (MP) inhibited the lipopolysaccharide-induced cytokine production in a dose-dependent manner. These results suggest the possible roles of activated monocytes/macrophages in the acute exacervation of MS and suppressive effect of MP on cytokine production by activated monocytes/macrophages.
 ...
PMID:[Cytokine production by peripheral blood monocytes/macrophages in the patients with multiple sclerosis and its suppression by methylprednisolone]. 162 50


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>