Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ozone (O3) is one of the major irritant oxidant gases in photochemical smog. In the present study, the in vitro effect of low concentrations of O3 (0.1 to 1 ppm) was evaluated on cell viability and cytokine secretion by alveolar macrophages (AM) from guinea pigs and healthy subjects. Cell injury was estimated immediately after O3 exposure by evaluation of ATP cell content (measured by bioluminescence) and lactic dehydrogenase (LDH) release in the culture medium. No cytotoxic effect was found: the ATP cell content of both guinea pig AM and human AM did not significantly change after O3 exposure and similarly the LDH release in the culture medium was unchanged. AM-derived cytokines (tumor necrosis factor alpha [TNF alpha], interleukin-1 beta [IL-1 beta], interleukin-6 [IL-6], and interleukin-8 [IL-8]) were evaluated in AM supernatants. O3 exposure was associated with a significant increase in cytokine secretion, with a peak value at 0.4 ppm O3. The exposure of the guinea pig AM to 0.4 ppm O3 for 60 min increased the IL-6 activity by 252 +/- 60% and TNF activity by 202 +/- 35%. The increase in monokine production by the human AM was 443 +/- 208% for TNF alpha, 484 +/- 171% for IL-1 beta, 383 +/- 147% for IL-6, and 226 +/- 45% for IL-8 after a 60-min exposure to 0.4 ppm O3. Lowest O3 concentrations (0.1 and 0.2 ppm) only increased TNF alpha secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Ozone stimulates synthesis of inflammatory cytokines by alveolar macrophages in vitro. 759 38

Three IL-1R antagonists (IL-1Ra) exist: secreted IL-1Ra and intracellular IL-1Ra (icIL-1Ra) types I and II. We have previously reported that human airway epithelial cells (HAEC) express icIL-1Ra type I, which can be up-regulated by corticosteroids. This study assessed whether cytokines and corticosteroids differentially effect icIL-1Ra type I protein release from HAEC to the extracellular compartment. We report that icIL-1Ra type I mRNA and intracellular protein are up-regulated in NCI-H292 cells, a human pulmonary mucoepidermoid carcinoma cell line, in response to IL-4, IL-13, IFN-gamma, and dexamethasone. The icIL-1Ra type I protein was detected in concentrated cell culture supernatants from NCI-H292 cells and normal human bronchial epithelial cells. The release of biologically relevant concentrations of active IL-1Ra from normal human bronchial epithelial cells was demonstrated by the ability of a neutralizing anti-IL-1Ra Ab to augment IL-1beta-mediated IL-8 secretion. IL-4, IL-13, and IFN-gamma induced immunoreactive IL-1Ra release into supernatants from NCI-H292 cells. Dexamethasone inhibited constitutive and cytokine-induced release of immunoreactive IL-1Ra. The release of icIL-1Ra type I protein was not related to cytotoxicity, as measured by lactate dehydrogenase. We propose that icIL-1Ra type I release from HAEC represents a novel mechanism by which IL-1 bioactivity in the airway microenvironment may be modulated. Cytokine-mediated icIL-1Ra type I synthesis may increase both intracellular protein and release to the extracellular space, where cell surface IL-1R can be antagonized. In contrast, corticosteroid-induced increases in icIL-1Ra type I synthesis and inhibition of extracellular protein release promote accumulation of icIL-1Ra type I protein within the intracellular compartment.
 ...
PMID:Extracellular release of the type I intracellular IL-1 receptor antagonist from human airway epithelial cells: differential effects of IL-4, IL-13, IFN-gamma, and corticosteroids. 919 Sep 49

In contrast to a mutant adhesin-deficient Streptococcus pyogenes (group A streptococcus), its isogenic parental strain binds to human keratinocytes and promotes a vigorous proinflammatory response, characterized by enhanced expression of several cytokines, a more rapid release of prostaglandin E2 (PGE2) and damage to keratinocyte membranes. However, adherence alone is not sufficient to induce these responses. In this study, we have begun to examine the contribution of other streptococcal products in interactions with keratinocytes by the construction and evaluation of mutants deficient in expression of the secreted pore-forming haemolysin, streptolysin O (SLO). Inactivation of SLO did not prevent the streptococci from adhering to cultured HaCaT keratinocytes or from expressing an unrelated second streptococcal haemolysin, streptolysin S, during infection of keratinocytes. As measured by a quantitative reverse transcriptase polymerase chain reaction (PCR) assay, inactivation of SLO also did not have a marked effect on the expression of interleukin 1alpha (IL-1alpha) during infection. However, the lack of the ability to produce SLO was associated with a considerable reduction in expression of IL-1beta, IL-6 and IL-8 by infected keratinocytes. Measurement of the release of PGE2 by an enzyme-linked immunosorbent assay demonstrated that the SLO-deficient mutants were also not capable of promoting the rapid high level of PGE2 release characteristic of the adherent SLO-producing parental strain. Finally, analyses using the fluorescent probe ethidium homodimer-1 and measurements of release of keratinocyte lactate dehydrogenase indicated that the failure of the SLO-deficient mutants to induce responses was associated with the failure of these mutants to damage the integrity of the keratinocyte membrane. These data implicate SLO as a factor that acts synergistically with an adhesin to modulate the signalling responses of keratinocytes during infection.
 ...
PMID:Streptolysin O and adherence synergistically modulate proinflammatory responses of keratinocytes to group A streptococci. 948 89

To evaluate the pathogenesis of high-altitude pulmonary edema (HAPE), we performed bronchoalveolar lavage (BAL) and pulmonary hemodynamic studies in seven patients with HAPE at its early stage. We measured cell counts, biochemical contents, and concentrations of pro-inflammatory cytokines including interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor (TNF)-alpha and of anti-inflammatory cytokines including IL-1 receptor antagonist (ra) and IL-10 in the BAL fluid (BALF). All patients showed increased counts for total cells, alveolar macrophages, neutrophils and lymphocytes, and markedly elevated concentrations of proteins, lactate dehydrogenase, IL-1beta, IL-6, IL-8, TNF-alpha and IL-1ra. The levels of IL-1alpha and IL-10 were not increased. Patients also showed pulmonary hypertension with normal wedge pressure. Both the driving pressure obtained as pulmonary arterial pressure minus wedge pressure and the PaO2 under room air were significantly correlated with the concentrations of IL-6 and TNF-alpha in the BALF. These findings suggest that the inflammatory cytokines play a role at the early stage of HAPE and might be related to pulmonary hypertension.
 ...
PMID:Inflammatory cytokines in BAL fluid and pulmonary hemodynamics in high-altitude pulmonary edema. 962 35

Extensively oxidized low density lipoprotein (ox-LDL), a modulator of atherogenesis, down-regulates the lipopolysaccharide (LPS)-induced activation of transcription factor NF-kappaB. We investigated whether 4-hydroxynonenal (HNE), a prominent aldehyde component of ox-LDL, represents one of the inhibitory substances. NF-kappaB activation by stimuli such as LPS, interleukin (IL)-1beta, and phorbol ester, but not tumor necrosis factor (TNF), was reversibly inhibited by HNE in a dose-dependent manner in human monocytic cells, whereas AP-1 binding was unaffected. Using similar HNE concentrations, LPS-induced kappaB- and TNF or IL-8 promoter-dependent transcription was prevented. Furthermore, pretreatment with HNE suppressed TNF production but not lactate dehydrogenase levels. Under these conditions the binding of LPS to monocytic cells was not significantly affected. However, induced proteolysis of the inhibitory proteins IkappaB-alpha, IkappaB-beta, and, at a later time point, IkappaB-epsilon was prevented. This is not due to inhibition of the proteasome, the major proteolytic activities of which remain unaffected, but rather to a specific prevention of the activation-dependent phosphorylation of IkappaB-alpha. This is the first report which demonstrates that HNE specifically inhibits the NF-kappaB/Rel system. Down-modulation of NF-kappaB-regulated gene expression may contribute at certain stages of atherosclerosis to low levels of chronic inflammation and may also be involved in other inflammatory/degenerative diseases.
 ...
PMID:4-Hydroxynonenal prevents NF-kappaB activation and tumor necrosis factor expression by inhibiting IkappaB phosphorylation and subsequent proteolysis. 1020 70

Nitrogen dioxide (NO(2)) is a common air pollutant outdoors and indoors in homes with unvented combustion sources. It is also a constituent of tobacco smoke. Epidemiological studies suggest that children exposed to NO(2), or living with smoking parents, have an increased incidence of respiratory viral infections. The most common virus causing severe respiratory symptoms in infants and young children is respiratory syncytial virus (RSV). In the present study we investigated whether NO(2) exposure affects RSV infection in airway epithelial cells, the host cells for viral replication and virus-induced cytokine production. Cultures of the bronchial epithelial cell line BEAS-2B exposed to 0.5, 1.0, and 1.5 ppm NO(2) for 60 min were infected with RSV. Viral replication, as well as RSV-induced interleukin (IL)-6 and IL-8, was assessed at various times postinfection. The NO(2) doses used were not toxic to the BEAS-2B cells as measured by release of lactic dehydrogenase (LDH). The internalization of RSV was increased by exposure to 0.5 ppm NO(2) and decreased by exposure to 1.5 ppm NO(2). On the other hand, the release of infectious virus 48 h postexposure was not affected by the two lower doses of NO(2), but was significantly reduced in cells exposed to 1.5 ppm NO(2). Virus-induced cytokine production was also significantly reduced in cells exposed to 1.5 ppm NO(2), and not affected by 0.5 and 1.0 ppm. It is likely that the decrease in cytokine production is related to the decrease in viral burden. These data suggest that possible increases in viral clinical symptoms associated with NO(2) may not be caused by increased susceptibility of the epithelial cells to infection but may result from effects of NO(2) on host defenses that prevent the spread of virus.
 ...
PMID:Effect of nitrogen dioxide on respiratory viral infection in airway epithelial cells. 1043 48

The main goal of the present study was to investigate the response of the human skin equivalent Apligraf in vitro to the application of irritant substances and its predictivity as a screening tool for cumulative skin irritant potential in humans. Vaseline, calcipotriol, trans-retinoic acid, and sodium lauryl sulfate were applied to Apligraf in vitro for 24 h. Cell viability (lactate dehydrogenase leakage), release and mRNA expression of the proinflammatory cytokines IL-1alpha and IL-8, and morphological changes were assessed. The same products were applied to 30 healthy volunteers in a double-blind, randomized, vehicle-controlled within-subject study. The skin reactions after repeated 24-h applications over 3 weeks under Finn chamber patches were monitored by visual scoring and biophysical methods (trans-epidermal water loss, chromametry, and blood flow). Sodium lauryl sulfate was cytotoxic to Apligraf, and increased the release and expression of cytokines at low (0.2%, 0. 4%), but not at high (0.8%, 1%) concentrations. It induced severe irritancy in vivo. Trans-retinoic acid increased the expression and release of cytokines with no detectable cytotoxicity and showed moderate irritancy in humans. Although calcipotriol did neither affect cell viability nor the production of cytokines, it induced morphological signs of irritation and was mildly irritant for healthy volunteers. Vaseline was innocuous in vivo and induced no changes in Apligraf. In conclusion, the cumulative skin irritation potential of the tested products could be predicted with Apligraf in a sensitive and specific manner, by monitoring cytotoxicity, proinflammatory cytokines, and morphological changes.
 ...
PMID:Use of human skin equivalent Apligraf for in vitro assessment of cumulative skin irritation potential of topical products. 1073 42

We present an adult patient with haemophagocytic syndrome (HPS) successfully treated with a combination of steroid pulse therapy and double filtration plasmapheresis (DFPP). A 58-year-old male was admitted with high fever, severe renal dysfunction, liver dysfunction and an increased level of lactate dehydrogenase. A serological test for Epstein-Barr (EB) virus showed an elevation of EBNA-IgM antibody titre. There were increased haemophagocytic histiocytes in the bone marrow in addition to thrombocytopenia and disseminated intravascular coagulation (DIC) accompanied by organ dysfunction. EB virus associated haemophagocytic syndrome was diagnosed. On admission, interferon (IFN)-gamma, interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor (G-CSF) and macrophage (M)-CSF were elevated, and were promptly normalized after steroid pulse therapy was initiated. G-CSF and M-CSF gradually decreased after DFPPs was started. To control hypercytokinaemia until treatment for the underlying disease is initiated, steroid pulse therapy and double filtration plasmapheresis are useful.
 ...
PMID:Virus-associated haemophagocytic syndrome responsive to steroid pulse therapy and double filtration plasmapheresis. 1093 Nov 70

This study was designed to investigate subacute effects of long-term exposure of both healthy and chronically inflamed human respiratory mucosa to ozone. Functional and metabolic effects on ciliary beat frequency (CBF), release of interleukin 8 (IL-8), interleukin 4 (IL-4), and gamma interferon (g-INF), as well as cellular viability and cytotoxicity, were monitored. Cell cultures of 60 specimens (healthy mucosa: n = 30, inflamed mucosa: n = 30) were exposed to synthetic air and to ozone-enriched synthetic air in different concentrations of 100, 500, and 1000 micrograms/m3. Continuous expositions were performed using an air/liquid interface cell culture technique for a period of 4 weeks. CBF was monitored using video-interference contrast microscopy and cytokine release was quantified by enzyme immunoassays. Cellular viability and cytotoxicity were controlled by measuring lactate dehydrogenase activity, cytosolic activity of esterases, and by staining of nuclear DNA. Synthetic air had no influence on CBF during the 4 weeks of exposure. IL-8 release was continuously diminished in unaffected and in chronically inflamed mucosa. Within the first week of continuous exposure with any ozone concentration neither CBF nor release of IL-8 were affected in healthy or in inflamed mucosa. During the second and the following weeks of exposure CBF and the release of IL-8 were reduced in both tissues. Release of IL-4 or g-INF were not detectable at any time during the 4 weeks of ozone exposure. At higher ozone concentrations of 500 and 1000 micrograms/m3 there was an increase of cytotoxicity which was greater in chronically inflamed than in healthy mucosa. In conclusion, ozone had no measurable effect on those parameters measured in human upper respiratory epithelium after one week of in vitro exposure to different concentrations, but did after longer periods of exposure. Chronically inflamed mucosa had a tendency toward a higher susceptibility to intermediate and high concentrations of ozone that did not reach a level of statistical significance under the conditions used in this study.
 ...
PMID:Subacute effects of ozone exposure on cultivated human respiratory mucosa. 1119 18

Enterotoxigenic B. fragilis, which produces a approximately 20 kD heat-labile toxin (BFT), has been associated with diarrhoeal diseases and mucosal inflammation. To determine if epithelial cells can contribute to BFT-induced inflammation, we assessed the expression of CXC chemokines by BFT-stimulated human intestinal epithelial cells. BFT stimulation increased expression of the neutrophil chemoattractant and activators ENA-78, GRO-alpha, and IL-8. Up-regulated chemokine mRNA expression was paralleled by increased protein levels. Activation of the IL-8 and NF-kappa B transcriptional reporters was inhibited in cells cotransfected with the I kappa B kinase beta and IkB alpha superrepressor plasmids. Whereas lactate dehydrogenase, which was used to monitor cell lysis, was released predominantly from the apical surface, CXC chemokines were predominantly secreted from the basolateral surface of BFT-treated epithelial cells. The basolateral secretion of CXC chemokines from BFT-stimulated colon epithelial cells suggests that these chemokines can contribute to the inflammatory cell infiltrate in the underlying intestinal mucosa.
 ...
PMID:Polarized secretion of CXC chemokines by human intestinal epithelial cells in response to Bacteroides fragilis enterotoxin: NF-kappa B plays a major role in the regulation of IL-8 expression. 1130 97


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