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)

Interleukin-6 signaling via its soluble receptor (sIL-6R) differentially regulates inflammatory chemokine expression and leukocyte apoptosis to coordinate transition from neutrophil to mononuclear cell infiltration. sIL-6R activities may, however, be influenced in vivo by the occurrence of two sIL-6R isoforms that are released as a consequence of differential mRNA splicing (DS) or proteolytic cleavage (PC) of the cognate IL-6R (termed DS- and PC-sIL-6R). Using human peritoneal mesothelial cells and a murine model of peritoneal inflammation, studies described in this work have compared the ability of both isoforms to regulate neutrophil recruitment. In this respect, DS- and PC-sIL-6R were comparable in their activities; however, these studies emphasized that IL-6 trans signaling differentially controls neutrophil-activating CXC chemokine expression. In vitro, stimulation of mesothelial cells with IL-6 in combination with either DS-sIL-6R or PC-sIL-6R showed no induction of CXC chemokine ligand (CXCL)1 (GRO alpha) and CXCL8 (IL-8), whereas both isoforms enhanced CXCL5 (ENA-78) and CXCL6 (granulocyte chemotactic protein-2) expression. Moreover, when complexed with IL-6, both isoforms specifically inhibited the IL-1 beta-induced secretion of CXCL8. These findings were paralleled in vivo, in which induction of peritoneal inflammation in IL-6-deficient (IL-6(-/-)) mice resulted in enhanced keratinocyte-derived chemokine and macrophage-inflammatory protein-2 (the murine equivalent of CXCL1 and CXCL8) levels, but reduced LPS-induced CXC chemokine (the murine equivalent of CXCL5) expression. Reconstitution of IL-6 signaling in IL-6(-/-) mice with IL-6 and its soluble receptor isoforms corrected this chemokine imbalance and suppressed overall neutrophil infiltration. These data confirm that sIL-6R-mediated signaling primarily limits neutrophil influx; however, induction of CXCL5 and CXCL6 may regulate other neutrophil responses.
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PMID:Differential regulation of neutrophil-activating chemokines by IL-6 and its soluble receptor isoforms. 1510 Mar 12

We previously described the physicochemical characteristics (particle size, adsorbed polynuclear aromatic hydrocarbons [PAHs], oxygen, and metal content) of butadiene soot (BDS) nanoparticles generated during incomplete combustion of the high-volume industrial petrochemical, 1,3-butadiene. We also demonstrated localization of BDS-delivered PAHs to lipid droplets of murine and human respiratory cells in vitro and up-regulation of biotransformation and oxidative stress responses in these cells. Here, the objective was to determine whether inhalation of BDS nanoparticles promotes up-regulation of Phase I biotransformation enzymes, oxidative stress responses, and inflammation in the lungs of mice. Female Balb/c mice exposed to BDS (5 mg/m(3), 4 h/d, 4 d) were killed immediately or 1 day after final exposure; bronchoalveolar lavage fluid (BALF) was collected from the lungs; total RNA was extracted from one lung and histopathology performed on the other. Histopathology and BALF analysis revealed particle-laden macrophages in airways of BDS-treated mice, accompanied by neutrophilia and epithelial damage. Microarray and qRT-PCR analyses revealed up-regulation of (1) aryl hydrocarbon receptor (AhR)-responsive genes: AhR repressor (Ahrr) and cytochrome P450 IA1 and IB1(Cyp1a1, Cyp1b1); (2) oxidative stress response genes: heme oxygenase 1 (Hmox1), nuclear factor erythroid-derived 2-like 2 (Nfe2l2), NADPH dehydrogenase quinone 1 (Nqo1), and glutathione peroxidase 2 (Gpx2); and (3) pro-inflammatory genes: interleukin-6 (IL-6), C-X-C motif ligand 2 (Cxcl2; analog to human IL-8) and ligand 3 (Cxcl3), and granulocyte chemotactic protein (Cxcl6). Inhalation of PAH-rich, petrochemical combustion-derived nanoparticles causes airway inflammation and induces expression of AhR-associated and oxidative stress response genes, as seen in vitro, plus pro-inflammatory genes.
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PMID:Soot nanoparticles promote biotransformation, oxidative stress, and inflammation in murine lungs. 1836 23

Acute inflammatory lesions of the placenta consist of diffuse infiltration of neutrophils at different sites in the organ. These lesions include acute chorioamnionitis, funisitis, and chorionic vasculitis and represent a host response (maternal or fetal) to a chemotactic gradient in the amniotic cavity. While acute chorioamnionitis is evidence of a maternal host response, funisitis and chorionic vasculitis represent fetal inflammatory responses. Intraamniotic infection generally has been considered to be the cause of acute chorioamnionitis and funisitis; however, recent evidence indicates that "sterile" intraamniotic inflammation, which occurs in the absence of demonstrable microorganisms induced by "danger signals," is frequently associated with these lesions. In the context of intraamniotic infection, chemokines (such as interleukin-8 and granulocyte chemotactic protein) establish a gradient that favors the migration of neutrophils from the maternal or fetal circulation into the chorioamniotic membranes or umbilical cord, respectively. Danger signals that are released during the course of cellular stress or cell death can also induce the release of neutrophil chemokines. The prevalence of chorioamnionitis is a function of gestational age at birth, and present in 3-5% of term placentas and in 94% of placentas delivered at 21-24 weeks of gestation. The frequency is higher in patients with spontaneous labor, preterm labor, clinical chorioamnionitis (preterm or term), or ruptured membranes. Funisitis and chorionic vasculitis are the hallmarks of the fetal inflammatory response syndrome, a condition characterized by an elevation in the fetal plasma concentration of interleukin-6, and associated with the impending onset of preterm labor, a higher rate of neonatal morbidity (after adjustment for gestational age), and multiorgan fetal involvement. This syndrome is the counterpart of the systemic inflammatory response syndrome in adults: a risk factor for short- and long-term complications (ie, sterile inflammation in fetuses, neonatal sepsis, bronchopulmonary dysplasia, periventricular leukomalacia, and cerebral palsy). This article reviews the definition, pathogenesis, grading and staging, and clinical significance of the most common lesions in placental disease. Illustrations of the lesions and diagrams of the mechanisms of disease are provided.
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PMID:Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance. 2742 50

Peritoneal metastasis (PM) is a very serious complication of gastrointestinal and gynecological malignancies which is poorly documented. Modified mesothelial cell layer and their microenvironments can favor fibrin deposition for cancer cell adhesion. Scanning and transmission electron microscopy of peritoneal surface and cancer cell clusters from cancer patients was done. Ascites and its impact on mesothelial cells were assessed by cytokine array. Neprilysin, matrix metalloprotease, epithelial mesenchymal transition (EMT) related molecules (E-cadherin, Snail, Slug, Twist, Vimentin and Fibronectin), tissues factor (TF), endothelial protein C receptors (EPCR) were quantified by q-PCR. Fibrin in the simples were stained using anti fibrin F1E1 antibody. Migration ability was assessed by scratch assay. Cell viability and neprilysin activity were analyzed by bioluminescence. Cancer cells-fibrin interaction was investigated by scanning electron microscopy (SEM) and microcinematography (MCG). Mesothelial cells change their morphology after incubation with carcinomatosis peritoneal fluids in vitro. EMT associated with upregulation of neprilysin, matrix metalloproteinase-2, tissue factor and cytokines secretions such as interleukin-6, and 8, hepatocyte growth factor and granulocyte chemotactic protein-2 mRNA and protein were observed. EPCR expression as a natural anticoagulant was decreased. In parallel, carcinomatosis cell clusters extracted from peritoneal fluids were found to be associated with fibrin. Kinetic analysis of cancer cell-fibrin interaction in vitro studied by MCG showed that fiber filaments generated from clots inhibited cancer cell adhesion on fibrin clots. These results indicated that fibrin deposit on the peritoneal surface serve as niches for cancer expansion in carcinomatosis patients.
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PMID:Fibrin Deposit on the Peritoneal Surface Serves as a Niche for Cancer Expansion in Carcinomatosis Patients. 3173 30