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)

Mouse peritoneal exudate cells induced by casein enhanced in vitro antibody production rate per cell of a hybridoma in co-culture. Culture supernatant of the exudate cells also enhanced three-fold the antibody productivity when added to cultures of a hybridoma at 10% (v/v). Hence the enhancement of antibody productivity by the exudate cells seemed to be caused by soluble enhancing factors secreted by the exudate cells. The exudate cells maximally secreted the enhancing factors when harvested from mice on day 4 of the induction period following the injection of casein. A semi-continuous culture of the hybridoma demonstrated the applicability of the culture supernatant to enhance antibody production by producing a two-fold increase over the control for seven days when supplemented with the supernatant at 5%. Significant amounts of interleukin-6 were detected in culture supernatant of the exudate cells. Interleukin-6 obtained from other sources enhanced the antibody productivity two-fold when added to the hybridoma culture at the concentration of 5 unit/ml. Interleukin-6, therefore, is expected to be one of the principal antibody enhancing factors secreted by the exudate cells. Other interleukins examined, that is, interleukin-1 to -5 did not enhance the antibody productivity.
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PMID:Enhancing effect of mouse peritoneal exudate cells and their products on antibody productivity of hybridoma cells: application of in vivo factors to in vitro culture. 136 11

Stromal cells of bone marrow origin produce a variety of known cytokines and some factors exhibiting apparently new biological activities. Several of these were identified by the study of cell to cell interactions and were not found in detectable amounts in media conditioned by the cells. We describe here a culture system that enables the release of stromal cytokines into medium free of any added proteins and supplemented with peptides from casein hydrolysate (0.1%). The absence of serum proteins allows extensive concentration and monitoring of activities that are otherwise undetectable. Stromal cells of the MBA-2.1 clonal cell line were seeded in a stationary bed reactor packed with a carrier of non-woven fabric matrix. After a proliferation phase with serum containing medium, the cells were maintained for over 10 months in protein-free medium. Throughout this extended incubation in the absence of serum or serum replacing proteins, stromal cells retained their viability and continuously released transforming growth factor-beta (TGF-beta), macrophage-colony stimulating factor (M-CSF) and restrictin-P, a cytotoxic factor that specifically arrested the growth of plasmacytoma cells. In addition, interleukin-6 (IL-6) was first undetectable, and later in culture its titer reached a maximum of 180,000 international units (IU)/ml. Concomitantly, the production of restrictin-P diminished and reached its lowest levels at the end of 10 months. The results may imply a possible causal relationship between the expression of IL-6 and restrictin-P, since no similarly significant changes were observed in the titers of M-CSF and TGF-beta. This novel bioreactor system may be adaptable for efficient production of different cytokines under absolute serum-free conditions.
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PMID:Dynamic changes in cytokine secretion by stromal cells during prolonged maintenance under protein-free conditions. 145 17

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.
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PMID:Phosphorylation of interleukin-6 at serine54: an early event in the secretory pathway in human fibroblasts. 161 Mar 48

Protein-energy malnutrition is associated with intrinsic defects in macrophage (MO) microbicidal function, but effects on MO-CD4+ cell interaction are unclear. This study examined the effect of protein-energy malnutrition on components of Ag presentation (AP) by peritoneal macrophages (PMO) and splenocyte responses (MLR) in the naive (resident) and infected state (mycobacterium-BCG), and assessed the potential role of prostaglandin (PGE2) and L-arginine-derived nitric oxide (NO) as regulatory mechanisms in these immune interactions. Mice were randomized to receive either a control (24% casein, RD) or low-protein (2.5% casein, LPD) diets for 8 weeks. PMO and splenocytes were harvested and AP function and MLR assessed +/- NG-mono-methyl-L-arginine (NMMA; competitive inhibitor of NO. synthesis) or indomethacin (PGE2 inhibitor). PMO components of AP were evaluated, including phagocytic function, MHC-class II (Ia) expression, and interleukin-1 (IL-1) and interleukin-6 (IL-6) production. PGE2 production and NO. (measured as NO-2) synthesis were also assessed. AP and MLR were preserved in protein-energy malnutrition in both resident and activated states. BCG infection in RD was associated with PMO activation as measured by increased O-2 and NO-2 release, but impaired AP and MLR responses. NMMA and indomethacin enhanced AP and MLR in RD groups only. Individual components of PMO AP (phagocytosis, IL-1 and IL-6 production) were defective during protein-energy malnutrition, as were NO-2 and PGE2 production. Thus, AP and MLR were preserved in LPD groups which may be related to a loss of prostaglandin- and L-arginine-mediated suppressor mechanisms.
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PMID:Antigen presentation in protein-energy malnutrition. 775 32

The neurotoxicant trimethyltin (TMT) increases mRNA levels for cytokines, tumor necrosis factor-alpha, interleukin-1alpha, and interleukin-6. Cytokines induce matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA). MMPs and uPA disrupt extracellular matrix. Since matrix damage may play a role in the neuropathological changes seen with TMT toxicity, we determined the effect of TMT on proteolytic enzyme production. Adult rats were injected with 8.0 mg TMT/kg. At different times after TMT injection, tissue samples from frontal lobe and hippocampus were assayed for MMPs and uPA, using gelatin-substrate and casein/plasminogen-substrate zymography. Gelatinase B (92 kDa type IV collagenase) production increased significantly in frontal lobe tissue at 24, 48 and 96 h, and in hippocampus at 48 h compared to saline-injected controls. Gelatinase A (72 kDa type IV collagenase) was significantly decreased at 12 and 24 h in frontal lobe compared to controls. Urokinase-type PA was significantly increased in hippocampus at 12 and 96 h, and in frontal lobe at 96 h compared to controls. Gelatinase B and uPA are up-regulated by TMT in frontal lobe and hippocampus, suggesting that they may contribute to the neuropathology of TMT.
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PMID:Trimethyltin induces gelatinase B and urokinase in rat brain. 921 29

To examine the effects of dietary glutamine on cytokine production by macrophages, mice were fed for 2 wk on a control diet that included 200.0 g casein/kg providing 19.6 g glutamine/kg or a glutamine-enriched diet that provided 54.8 g glutamine/kg partly at the expense of casein. There were no differences in weight gain between animals fed the two diets. The plasma concentrations of a number of amino acids differed according to the diet fed; this variation largely reflected the variation in the levels of the different amino acids in the diets. Plasma glutamine concentration was not significantly affected by dietary glutamine level. The production of three cytokines, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6, was greater for lipopolysaccharide-stimulated macrophages from mice fed the glutamine-enriched diet. Thus, increasing the amount of glutamine in the murine diet enhances the ability of macrophages to respond to stimulation, at least in terms of cytokine production. These observations suggest that increasing the availability of glutamine orally could promote immune responses involving macrophage-derived cytokines.
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PMID:Dietary glutamine enhances cytokine production by murine macrophages. 1067 40

Porphyromonas gingivalis is a primary etiological agent of generalized severe periodontitis, and emerging data suggest the importance of reactive oxygen and nitrogen species in periodontal tissue damage, as well as in microbial killing. Since nitric oxide (NO) released from inducible NO synthase (iNOS) has been shown to possess immunomodulatory, cytotoxic, and antibacterial effects in experimental models, we challenged iNOS-deficient (iNOS(-/-)) mice with P. gingivalis by using a subcutaneous chamber model to study the specific contribution of NO to host defense during P. gingivalis infection. iNOS(-/-) mice inoculated with P. gingivalis developed skin lesions and chamber rejection with higher frequency and to a greater degree than similarly challenged C57BL/6 wild-type (WT) mice. Chamber fluid from iNOS(-/-) mice possessed significantly more P. gingivalis than that of WT mice. The immunoglobulin G responses to P. gingivalis in serum was similar in WT and iNOS(-/-) mice, and the inductions of tumor necrosis factor alpha, interleukin-1 beta and interleukin-6, and prostaglandin E(2) were comparable between the two mouse strains. Although no differences in total leukocyte counts in chamber fluids were observed between iNOS(-/-) and WT mice, the percentage of dead polymorphonuclear leukocytes (PMNs) was significantly greater in iNOS(-/-) mouse chamber fluids than that of WT samples. Interestingly, casein-elicited PMNs from iNOS(-/-) mice released more superoxide than did WT PMNs when stimulated with P. gingivalis. These results indicate that modulation of superoxide levels is a mechanism by which NO influences PMN function and that NO is an important element of the host defense against P. gingivalis.
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PMID:Mice lacking inducible nitric oxide synthase demonstrate impaired killing of Porphyromonas gingivalis. 1293 33

Leptin and its receptors have been shown to be expressed in several tissues, suggesting that this protein might be effective not only at the CNS level but also peripherally. We have previously reported that leptin and its long form receptor are expressed in the mouse mammary epithelial cell line HC11. In this study, we report a specific relationship among leptin, prolactin (PRL), interleukin-6 (IL-6), and tumor necrosis-alpha (TNF-alpha) in the modulation of the suppressor of cytokine signaling 1 (SOCS-1). Furthermore, we show that leptin and PRL are able to effectively enhance SOCS-1 gene expression in the HC11 cell line. Finally, high concentrations of leptin (100 nM) and/or PRL significantly (p<0.05) reduce the inhibitory effect of IL-6 (10 and 100 ng/ml) and TNF-alpha (10 and 100 ng/ml) on beta-casein gene expression in HC11 cells transfected with pbetacCAT, a chimeric rat-beta casein gene promoter-cloramphenicol acetyl transferase (CAT) gene construct. These results provide evidence that leptin may be an important mediator in regulating mammary gland growth and development and that this role may be related to the immune factors that are involved in inflammation.
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PMID:Leptin and prolactin modulate the expression of SOCS-1 in association with interleukin-6 and tumor necrosis factor-alpha in mammary cells: a role in differentiated secretory epithelium. 1525 87

The CNS can be activated by both local and systemic inflammation, resulting in the manifestation of sickness symptoms. The pathways by which the CNS is activated under these two conditions, however, may differ. In this study, we injected casein into the peritoneal cavity (i.p.) or into an s.c. air pouch of mice to induce restricted local inflammation. Both routes of casein injection caused fever and reduced locomotor activity. These responses were not accompanied by the statistically significant induction of the inflammatory cytokine interleukin-1 (IL-1) in the blood and brain. Further, these responses were produced without the induction of brain cyclooxygenase-2 (COX-2), which has been implicated as an obligatory step in systemic inflammation-induced activation of the CNS. Induction of IL-1, interleukin-6 (IL-6), and COX-2, however, was found consistently at the sites of casein injection. The local inflammation-induced febrile and locomotor activity responses were blunted in animals deficient in functional Toll-like receptor 4 (TLR4), type I interleukin-1 receptor (IL-1R1), IL-6, or COX-2. Therefore, the observed febrile and locomotor activity effects appear to require local, but not central, IL-1, IL-6, and COX-2. These findings suggest that local inflammation can activate the CNS via pathways distinguishable from those mediating systemic inflammation-induced CNS activation.
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PMID:Localized inflammation in peripheral tissue signals the CNS for sickness response in the absence of interleukin-1 and cyclooxygenase-2 in the blood and brain. 1895 Jun 89

Enterococcus faecium is an emerging pathogen that causes infections in hospitalized patients with various co-morbid diseases. These underlying diseases are often associated with an acute-phase response that renders patients vulnerable to nosocomial infections. To study the influence of the acute-phase response induced by sterile tissue injury on host defence against E. faecium, mice were injected subcutaneously with either turpentine or casein 1 day before intraperitoneal infection with E. faecium. Control mice were subcutaneously injected with saline or sodium bicarbonate, respectively. Turpentine and casein induced an acute-phase response as reflected by increases in the plasma concentrations of interleukin-6, serum amyloid P and C3. A pre-existent acute-phase response in mice was associated with a strongly reduced capacity to clear E. faecium, resulting in prolonged bacteraemia for several days. The inflammatory response to E. faecium was impaired in mice with an acute-phase response, as shown by reduced capacity to mount a neutrophilic leucocytosis in peripheral blood and by decreased local cytokine concentrations. These data indicate that the acute-phase response impairs host defence against E. faecium, suggesting that this condition may contribute to the increased vulnerability of critically ill patients to enterococcal infections.
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PMID:The acute-phase response impairs host defence against Enterococcus faecium peritonitis. 1917 94


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