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)

Calcitonin precursors (CTpr), including procalcitonin, are important markers and also potentially harmful mediators in response to microbial infections. The source and function of CTpr production in sepsis, however, remains an enigma. In the classical view, the transcription of the CT-I gene is restricted to neuroendocrine cells, in particular the C cells of the thyroid. To better understand the pathophysiology of CTpr induction in sepsis, we used an animal model analog to human sepsis, in which bacterial infection is induced in hamsters by implanting Escherichia coli pellets ip. Compared with control hamsters, levels of CTpr were elevated several fold in septic plasma and in nearly all septic hamster tissues analyzed. Unexpectedly, CT-messenger RNA was ubiquitously and uniformly expressed in multiple tissues throughout the body in response to sepsis. Notably, the transcriptional expression of CT-messenger RNA seemed more widely up-regulated in sepsis than were classical cytokines (e.g. tumor necrosis factor-alpha and interleukin-6). Our findings, which describe a potentially new mechanism of host response to a microbial infection mediated by CTpr, introduce a new pathophysiological role for the CT-I gene.
 ...
PMID:Ubiquitous expression of the calcitonin-i gene in multiple tissues in response to sepsis. 1123 31

In a phase IV, open-label study, 25 patients with clinically stable chronic sinusitis and persistent maxillary sinus inflammation were treated for 14 days with clarithromycin 500 mg twice daily. Biopsy specimens of the maxillary sinus mucosa were obtained pretreatment and evaluated for macrophages (CD68), eosinophils (MBP), elastase, interleukin-6 (IL-6), IL-8, tumor necrosis factor-alpha (TNF-alpha), and activity of eosinophils (EG2), as well as edema score. Clinical signs and symptoms were assessed pretreatment, at the end of treatment, and 1 and 2 weeks later. Statistically significant reductions (P < or = .05) from pretreatment were observed for all markers of sinus mucosal inflammation, including CD68, EG2, elastase, IL-6, IL-8, TNF-alpha, and edema score, with a trend to decreased total eosinophil count. Improvement was observed for all clinical signs and symptoms of chronic sinusitis--sinus pain, sinus headache, nasal congestion, nasal discharge, and mucopurulent discharge--up to 14 days after the end of treatment. Cultures to evaluate persistent infection with Chlamydia pneumoniae showed negative results. Significant reductions in various markers of sinus mucosal inflammation support the role of clarithromycin in modulating immunologic responses. Improvement of clinical signs and symptoms in patients with chronic inflammatory sinusitis not meeting criteria for known or presumed bacterial infection was also noted up to 2 weeks after completion of a 14-day course of clarithromycin.
 ...
PMID:Anti-inflammatory activity of clarithromycin in adults with chronically inflamed sinus mucosa. 1144 71

To assess the potential role of interleukin-6 (IL-6) in the pathogenesis of dengue virus infection, levels of this cytokine were measured in children with dengue virus infection on admission to the hospital. As presumed surrogate markers of IL-6, C-reactive protein (CRP) and secretory phospholipase A2 (sPLA2) were measured. Three groups were studied: 33 apparently healthy children as negative controls, 11 children with bacterial infections as positive controls, and 186 children with serologically documented dengue virus infection. One-hundred and fifteen patients had dengue fever (DF) and 71 had dengue hemorrhagic fever (DHF). Compared with healthy controls, dengue shock syndrome (DSS) patients had significantly higher levels of IL-6 on admission (P < 0.05), comparable with those in positive controls. Dengue patients with shock had significantly higher levels of IL-6 than normotensive patients (P < 0.001) and higher levels of IL-6 were associated with a higher incidence of ascites. C-reactive protein concentrations in dengue patients and in healthy children were not different, but lower than in children with bacterial infections (P = 0.008). Secretory phospholipase A2 levels were higher in dengue patients than in apparently healthy children (P < or = 0.05) and similar to those in children with bacterial infection. Dengue shock syndrome patients had significantly higher sPLA2 concentrations than normotensive patients (P = 0.02). These data indicate that IL-6 and sPLA2 may have a pathogenetic role only in the most severe forms of dengue virus infection.
 ...
PMID:Inflammatory mediators in dengue virus infection in children: interleukin-6 and its relation to C-reactive protein and secretory phospholipase A2. 1150 11

Calorie restriction (CR) is known to prolong the life span and maintain an active immune function in aged mice, but it is still not known if rodents under CR can respond optimally to bacterial infection. We report here on the influence of CR on the response of peritoneal macrophages to lipopolysaccharide, splenic NF-kappaB and NF-interleukin-6 (IL-6) activities, and mortality in polymicrobial sepsis induced by cecal ligation and puncture (CLP). Macrophages from 6-month-old C57BL/6 mice on a calorie-restricted diet were less responsive to lipopolysaccharide, as evidenced by lower levels of IL-12 and IL-6 protein and mRNA expression. Furthermore, in vitro lipopolysaccharide-stimulated macrophages from mice under CR also expressed decreased lipopolysaccharide receptor CD14 levels as well as Toll-like receptor 2 (TLR2) and TLR4 mRNA levels. In addition, the phagocytic capacity and class II (I-A(b)) expression of macrophages were also found to be significantly lower in mice under CR. Mice under CR died earlier (P < 0.005) after sepsis induced by CLP, which appeared to be a result of increased levels in serum of the proinflammatory cytokines tumor necrosis factor alpha and IL-6 and splenic NF-kappaB and NF-IL-6 activation 4 h after CLP. However, mice under CR survived significantly (P < 0.005) longer than mice fed ad libitum when injected with paraquat, a free radical-inducing agent. These data suggest that young mice under CR may be protected against oxidative stress but may have delayed maturation of macrophage function and increased susceptibility to bacterial infection.
 ...
PMID:Effects of calorie restriction on polymicrobial peritonitis induced by cecum ligation and puncture in young C57BL/6 mice. 1152 18

C-reactive protein (CRP) is an acute-phase protein featuring a homopentameric structure and Ca-binding specificity for phosphocholine (PCh). Expression of CRP is regulated mainly at the transcriptional level with interleukin-6 being the principal inducer of the gene during the acute phase. The crystal structure of CRP has been determined and the topology and chemical composition of its ligand-binding site determined. The wide distribution of PCh in polysaccharides of pathogens and in cellular membranes allows CRP to recognize a range of pathogenic targets as well as membranes of damaged and necrotic host cells. CRP bound to a multivalent ligand can efficiently initiate the assembly of a C3 convertase through the classical pathway and thus decorate the surface of the ligand with opsonic complement fragments. However, the protein does not favor the formation of a C5 convertase and therefore, CRP-initiated complement activation does not mediate acute inflammatory reactions and membrane damage. CRP also interacts with Fc receptors on phagocytic cells and acts as an opsonin. Other CRP-initiated signals through interactions with neutrophil Fc receptors have an overall anti-inflammatory effect. Thus, the main biological function of CRP appears to be host defense against bacterial pathogens and clearance of apoptotic and necrotic cells. Protection from lethal bacterial infection, from complement-induced alveolitis, and from endotoxemia has been confirmed in vivo using transgenic mice. Additional functions, including participation in atherogenesis and pathogenesis of myocardial injury after myocardial infarction have been reported. However, the weight of the evidence is that CRP like other acute-phase proteins is a component first line of innate host defense.
 ...
PMID:Human C-reactive protein: expression, structure, and function. 1153 80

Toll-like receptors (TLRs) are a family of pattern recognition receptors that are critical for cellular responses to a variety of bacterial, viral, and fungal products. Mast cells are important to host survival in a number of models of bacterial infection and might act as sentinel cells in host defense. We therefore examined the expression of TLRs and associated molecules by murine bone marrow-derived mast cells (BMMCs). BMMCs and the murine mast cell line MC/9 expressed mRNA for TLR2, TLR4, and TLR6 but not TLR5 and for both adapter molecule MD-2 and signaling molecule MyD88 but lacked surface CD14. After activation with the TLR2- and TLR4-dependent stimuli Staphylococcus aureus-derived peptidoglycan and Escherichia coli-derived lipopolysaccharide (LPS), respectively, mast cells produced significant levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha). To determine whether mast cells require TLR4 for cellular responses to LPS, mast cells were derived from the bone marrow cells of C3H/HeJ and C57Bl/10ScNCr mice containing a point mutation and a null mutation, respectively, in TLR4. Using these models, we demonstrated that the BMMC IL-6 and TNF-alpha responses to LPS were completely dependent on functional TLR4 with no significant LPS response observed in its absence. These findings have important implications for the mechanism of mast cell responses to pathogens and their products and suggest that different TLR4-expressing cells might have different thresholds for activation with LPS.
 ...
PMID:Toll-like receptor 4-mediated activation of murine mast cells. 1173 61

Bacterial infection results in inflammatory responses that may lead to soft-tissue damage and bone resorption. However, the mechanisms by which different bacteria contribute to lesions of endodontic origin are not fully understood. This study examined the response to Streptococcus mutans and Porphyromonas endodontalis in two cell types that are involved in periapical pathology, mononuclear and osteoblastic cells. This was accomplished by measuring the induction of chemokines (monocyte chemoattractant protein-1, macrophage inflammatory protein-2) and proinflammatory cytokines (interleukin-1beta, tumor necrosis factor-alpha, interleukin-6, interferon-gamma). The results demonstrated that S. mutans more efficiently stimulate inflammatory cytokine production by mononuclear cells, whereas P. endodontalis is relatively more potent in activating osteoblastic cells. Moreover, optimal activation of osteoblastic cells by S. mutans requires soluble mediators produced by mononuclear cells, whereas P. endodontalis does not. These results suggest that the association of different bacteria with specific pathologic processes may be partially explained by their capacities to activate specific host cells.
 ...
PMID:An optimal host response to a bacterium may require the interaction of leukocytes and resident host cells. 1204 63

Interleukin-6 family cytokines have been implicated in adaptive and innate immunity, hematopoiesis, and inflammation. This cytokine family shares a signal-transducing receptor subunit called gp130. gp130(F759/F759) knockin mice carry a point mutation at the SHP2-binding site of gp130 due to the replacement of tyrosine-759 (Y759 for human gp130) with phenylalanine (F). To explore the effect of this point mutation on the host response to bacterial infection, gp130(F759/F759) knockin mice were infected with Listeria monocytogenes. gp130(F759/F759) knockin mice began to die at 3 to 4 days post infection (p.i.) and showed higher mortality than did controls. Listeria titers at 3 days p.i. in the peritoneal cavity, spleen, and liver were significantly higher in gp130(F759/F759)knockin mice than in controls. Nitric oxide production, upregulation of the mRNA levels of a variety of cytokines, and listericidal activity in gp130(F759/F759) macrophages were unchanged. However, gp130(F759/F759) knockin mice displayed significantly lower levels of interferon (IFN)gamma in serum and in the culture supernatant from peritoneal exudate cells and splenocytes, in response to Listeria infection. These results suggest that the Y759 point mutation in gp130 attenuates the early phase of defense against Listeria infection, possibly owing to insufficient elevation of IFNgamma levels, and thus gp130 is a possible candidate gene for Listeria susceptibility.
 ...
PMID:Tyrosine 759 of the cytokine receptor gp130 is involved in Listeria monocytogenes susceptibility. 1207 Jul 75

Even though cigarette smoking has been shown to suppress immune responses in the lungs, little is known about the effect of cigarette smoke components on respiratory infections. In the present study, the effects of cigarette smoke condensate (CSC) on bacterial replication in alveolar macrophages and the immune responses of macrophages to infection were examined. Furthermore, a possible immunotherapeutic effect of epigallocatechin gallate (EGCg), a major form of tea catechins, on the CSC-induced suppression of antimicrobial activity and immune responses of alveolar macrophages was also determined. The treatment of murine alveolar macrophage cell line (MH-S) cells with CSC significantly enhanced the replication of Legionella pneumophila in macrophages and selectively down-regulated the production of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) induced by bacterial infection. The treatment of macrophages with EGCg not only overcame the CSC-induced suppression of antimicrobial activity but also strengthened the resistance of macrophages to infection. EGCg also markedly up-regulated the CSC-suppressed IL-6 and TNF-alpha production by macrophages in response to infection. The results of exogenous TNF-alpha treatment and neutralization treatment with anti-TNF-alpha and anti-gamma-interferon (IFN-gamma) antibodies and the determination of IFN-gamma mRNA levels indicate that CSC-suppressed macrophages can be activated by EGCg to inhibit L. pneumophila growth by up-regulation of TNF-alpha and IFN-gamma production. Thus, this study revealed that CSC selectively alters the immune responses of macrophages to L. pneumophila infection and leads to an enhancement of bacterial replication in macrophages. In addition, the tea catechin EGCg can diminish such suppressive effects of CSC on alveolar macrophages.
 ...
PMID:Epigallocatechin gallate, a potential immunomodulatory agent of tea components, diminishes cigarette smoke condensate-induced suppression of anti-Legionella pneumophila activity and cytokine responses of alveolar macrophages. 1209 87

The pathogenesis of filarial limb edema is not known. The role of parasitological variables and parasite-mediated phenomena in the development of limb edema was investigated in the Presbytis entellus-Brugia malayi model. Infection was initiated with subcutaneous inoculation of infective third-stage larvae (L(3)), and the animals were reexposed to different doses of L(3) at the prepatent, patent, and diminishing microfilaremia (0 to 5% of peak microfilaremia count) stages of infection. A large L(3) inoculum size and repeated inoculation in the ankle region during the prepatent, patent, and diminishing microfilaremia stages of infection were found to be necessary for reproducible induction of limb edema. The preadult stage of the parasite was found to be the most potent inducer of limb edema, followed by L(5) and L(4). The presence of the proinflammatory cytokines tumor necrosis factor alpha, interleukin-1beta, and interleukin-6 in edema fluid in the leg receiving the parasite challenge indicated that the limb edema development was due to parasite-mediated cytokine responses. The absence of bacterial infection or anti-streptolysin O titer in the edema fluid and blood indicated that bacterial infection is not necessary for the development of limb edema.
 ...
PMID:Preadult stage parasites and multiple timed exposure to infective larvae are involved in development of limb edema in Brugia malayi-infected Indian leaf monkeys (Presbytis entellus). 1209 95


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