Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When macrophages were cultured with lactoferrin, cytokines such as tumor necrosis factor (TNF-alpha), interleukin 8 (IL-8) and nitric oxide (NO) were secreted. Secretion of TNF-alpha peaked at 6 h of incubation in the presence of lactoferrin and then declined. About 80% of the maximum secretion of IL-8 was observed at 6 h of incubation. The concentration of IL-8 in the culture medium remained almost constant between 24-72 h. In contrast, no significant effect on NO secretion was observed at 6 h, but a significant effect was observed at 24 h and secretion gradually increased between 24-72 h. The effects of lactoferrin on the secretion of TNF-alpha, IL-8 and NO were dose-dependent and lactoferrin had a significant effect on secretion of at concentrations greater than 10 mg/ml. The use of reverse transcription-polymerase chain reaction (RT-PCR) showed that the results obtained were consistent with the cytokine secretion results. It is concluded that lactoferrin activates macrophages which result in the secretion of TNF-alpha, IL-8 and NO.
Biochem Mol Biol Int 1997 Sep
PMID:Activation of macrophages by lactoferrin: secretion of TNF-alpha, IL-8 and NO. 931 85

Air pollution, in particular that generated by road traffic, is a matter of rising public concern and has been implicated in the worsening of asthma. In this article, the evidence that air pollutants (particularly sulphur dioxide, ozone and nitrogen dioxide) can affect the airways of asthmatic patients is reviewed, and the possible molecular mechanisms that may link air pollution to increased inflammation in the airways are discussed. Airway epithelial cells may respond to oxidant pollutants by the activation of transcription factors, such as nuclear factor kappa B, resulting in increased transcription of genes for certain cytokines, such as interleukin 8 and inflammatory enzymes, such as inducible nitric oxide synthase and cyclo-oxygenase.
Mol Med Today 1995 Jun
PMID:Air pollution and asthma: molecular mechanisms. 941 51

Chronic hemodialysis (HD) patients have defects in cell-mediated immunity. To investigate the mechanisms underlying this immunodeficiency, we studied the production of cytokines in peripheral blood mononuclear cells (PBMC) from HD patients. PBMC from 22 HD patients and 20 healthy controls were cultured for 48 h in the presence or absence of phytohemagglutinin (PHA), lipopolysaccharide (LPS), or tuberculin purified protein derivative (PPD). Cytokine levels were measured by enzyme-linked immunosorbent assays. Only 64% of HD patients had a positive tuberculin skin test compared to 90% of normal Japanese controls. HD patients showed a diminished proliferative response to PHA. Compared to healthy controls, stimulated PBMC from HD patients produced similar amounts of T cell-derived cytokines (interleukin-2 (IL-2) and interferon-gamma (IFN-gamma)), but greater amounts of monocyte-derived inflammatory cytokines (IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), and IL-8) and a regulatory cytokine (IL-10). IL-10 production was positively correlated with IL-1 beta and TNF-alpha in healthy controls, whereas no correlation was observed in HD patients. Abnormal cytokine production by monocytes may contribute to the immunodeficiency seen in HD patients.
Res Commun Mol Pathol Pharmacol 1997 Oct
PMID:Increased production of interleukin-10 and inflammatory cytokines in blood monocytes of hemodialysis patients. 943 12

We measured the plasma levels of anti-inflammatory cytokines, including interleukin 1 receptor antagonist (IL-1ra), IL-4 and IL-10; inflammatory cytokines, including IL-2, IL-6, IL-8 and tumor necrosis factor receptor I and II (TNFR I and TNFR II); and endotoxin in 11 patients with septic shock associated with gram-negative bacteria and 12 patients with sepsis not associated with shock. The plasma levels of IL-1ra and IL-10 were elevated in the septic shock group compared with the sepsis group. TNFR I and TNFR II levels tend to be higher in the septic shock group. The plasma level of TRNF-alpha was significantly correlated with levels of IL-1ra, IL-4, IL-10, TNFR I, and TNFR II. The elevated levels of the anti-inflammatory cytokines, TNFR I, and TNFR II, appeared to reflect an attempt to suppress the shock syndrome.
Res Commun Mol Pathol Pharmacol 1997 Oct
PMID:Anti-inflammatory cytokine levels in patients with septic shock. 943 13

Gaucher disease, the most common glycolipid storage disease, is caused by glucocerebrosidase deficiency, resulting in accumulation of glucocerebrosides within the macrophages of the reticuloendothelial system. The disease is characterized by great phenotypic heterogeneity, which can be explained only in part by the various mutations in the glucocerebrosidase gene, and by the amount of storage material in affected organs and tissues. Therefore, it has been postulated that some of the biochemical and clinical features may be related to the fact that "Gaucher" cells, as activated macrophages, express and release cytokines such as IL-1beta, IL-8, IL-6 and TNF-alpha which play a role in different physiological processes. In the present study, cytokine mRNA expression was measured in monocytes isolated from Gaucher patients and from healthy controls, using RT-PCR methodology with semiquantitative analysis. We found significantly increased expression of IL-1beta mRNA, as well as a trend to elevated TNF-alpha mRNA in Gaucher patients relative to healthy individuals. There were no statistically significant differences between Gaucher disease patients and controls with respect to two other tested cytokines (IL-6 and IL-8).
Blood Cells Mol Dis 1997 Dec
PMID:Cytokine mRNA in Gaucher disease. 944 53

Interleukin (IL)-8 is a C-X-C chemokine that potently chemoattracts and activates neutrophils. We determined whether IL-8 could be produced by human airway smooth muscle cells in culture and examined its regulation. TNF-alpha stimulated IL-8 mRNA expression and protein release in a time- and dose-dependent manner, whereas IFN-gamma alone had no effect. Both cytokines together did not induce greater IL-8 release compared to TNF-alpha alone. IL-1beta was more potent in inducing IL-8 release and, together with TNF-alpha, there was a synergistic augmentation of IL-8 release. IL-8 release induced by TNF-alpha and IFN-gamma was partly inhibited by the Th-2-derived cytokines IL-4, IL-10, and IL-13, as well as by dexamethasone. In addition to its contractile responses, airway smooth muscle cells have synthetic and secretory potential with the release of IL-8 and subsequent recruitment and activation of neutrophils in the airways. Release of IL-8 can be modulated by Th-2-derived cytokines and corticosteroids.
Am J Respir Cell Mol Biol 1998 Jan
PMID:Expression and release of interleukin-8 by human airway smooth muscle cells: inhibition by Th-2 cytokines and corticosteroids. 944 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.
Mol Microbiol 1998 Jan
PMID:Streptolysin O and adherence synergistically modulate proinflammatory responses of keratinocytes to group A streptococci. 948 89

A critical feature of sepsis-induced adult respiratory distress syndrome (ARDS) is the release of cytokines (such as interleukin [IL]-6, IL-8, and tumor necrosis factor [TNF]) from endotoxin (lipopolysaccharide [LPS])-activated alveolar macrophages (AM). Nuclear factor kappa B (NF-kappaB) is activated in AM from patients with ARDS, and it is essential for the transcription of many cytokine genes. In these studies, we evaluated the regulation of LPS-induced cytokine release and the activation of NF-kappaB in human AM. We found that the activation of NF-kappaB and the release of IL-6, IL-8, and TNF from AM exposed to LPS was protein kinase C-independent and tyrosine kinase- and phosphatidylcholine-specific phospholipase C-dependent. We also found that LPS-induced activation of NF-kappaB was enhanced in AM cultured in serum or in the presence of LPS-binding protein, simulating conditions in the lung that are present in ARDS. In addition, LPS triggered the activation of several different NF-kappaB complexes in AM, and different forms of NF-kappaB bound to the IL-6, IL-8, and TNF promoter sequences. These observations suggest that physiologic abnormalities present in the lungs of patients with ARDS facilitate the activation of NF-kappaB and local release of cytokines.
Am J Respir Cell Mol Biol 1998 Mar
PMID:Lipopolysaccharide-induced NF-kappaB activation and cytokine release in human alveolar macrophages is PKC-independent and TK- and PC-PLC-dependent. 949 Jun 56

Neutrophil accumulation and activation of the complement system with subsequent deposition of the cytolytic membrane attack complex (MAC) have been implicated in the pathogenesis of myocardial ischemia/reperfusion injury. The MAC, when present in high concentrations, promotes target cell lysis. However, relatively little is known about the potential modulatory role of sublytic concentrations of the MAC on nucleated cell function in vivo. In vitro studies demonstrated that the MAC regulates cell function by promoting the expression of pro-inflammatory mediators, including adhesion molecules and pro-inflammatory cytokines. We examined, using C6-deficient and C6-sufficient rabbits, the regulatory role of the MAC in mediating IL-8 expression and subsequent neutrophil recruitment in the setting of myocardial ischemia/reperfusion injury. C6-deficient and C6-sufficient rabbits were subjected to 30 min of regional myocardial ischemia followed by a period of reperfusion. In addition to a significant reduction in myocardial infarct size in C6-deficient animals, analysis of myocardial tissue demonstrated a decrease in neutrophil influx into the infarcted region. The reduction in neutrophil influx correlated with the decreased expression of the neutrophil chemotactic cytokine IL-8, as determined by ELISA and immunohistochemical analysis. The results derived from this study provide evidence that the MAC has an important function in mediating the recruitment of neutrophils to the reperfused myocardium through the local induction of IL-8.
J Mol Cell Cardiol 1998 Jan
PMID:Attenuation of interleukin-8 expression in C6-deficient rabbits after myocardial ischemia/reperfusion. 950 Aug 66

Cardiac myxoma cells produce large amounts of interleukin (IL)-6 and IL-8. To determine whether immunosuppressive agents could be used to treat cardiac myxoma, we tested the effects of dexamethasone and three of the newer second-generation immunosuppressive drugs, cyclosporin A, tacrolimus, and deoxyspergualin, on the production of IL-6 and IL-8 in these cells. Cultured cardiac myxoma cells were used as in vitro model of cardiac myxoma. Cells were tested for 24 hours with 10(-7) M dexamethasone, 10(-6) M cyclosporin A, 10(-8) M tacrolimus, and 10(-6) M 15-deoxyspergualin, with aliquots of conditioned medium being assayed for cytokine levels at 0, 6, 12, and 24 hours. Cardiac myxoma cells isolated from 4 patients all produced quantities of IL-6 and IL-8. The concentrations of IL-6 in the medium after 7 days in culture ranged from 79,000 to 2,740,000 pg/ml, and the concentrations of IL-8 ranged from 40,000 to 1,000,000 pg/ml. Exposure of cyclosporin A and dexamethasone almost completely inhibited the production of IL-6 and IL-8 after 24 hours of treatment. Tacrolimus inhibited the production of both cytokines by 55%, while 15-deoxyspergualin reduced IL-6 levels by 24% and IL-8 levels by 48% after separate 24 hour treatments. These results suggest that these newer immunosuppressive agents may be useful in reducing the production of IL-6 and IL-8 in patients with cardiac myxoma.
Res Commun Mol Pathol Pharmacol 1997 Jul
PMID:Immunosuppressive drugs inhibit the production of interleukin-6 and interleukin-8 in cultured cardiac myxoma cells. 950 69


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