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

In this work we analyzed the roles of meningococcal lipooligosaccharide (LOS) and capsule expression in the interaction of Neisseria meningitidis with human dendritic cells (DC). Infection of DC with serogroup B wild-type meningococci induced a strong burst of the proinflammatory cytokines and chemokines tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-8. In contrast, a serogroup B mutant strain lacking LOS expression barely led to cytokine induction, demonstrating that meningococcal LOS is the main mediator of the proinflammatory response in human DC. Sialylation of meningococcal LOS did not influence cytokine secretion by DC. However, we found the phagocytosis of N. meningitidis by human DC to be inhibited by LOS sialylation. In addition, the expression of the meningococcal serogroup A, B, and C capsules dramatically reduced DC adherence of N. meningitidis and phagocytosis to some extent. Hence, LOS sialylation and capsule expression are independent mechanisms protecting N. meningitidis from the phagocytic activity of human DC.
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PMID:Lipooligosaccharide and polysaccharide capsule: virulence factors of Neisseria meningitidis that determine meningococcal interaction with human dendritic cells. 1195 82

Bluetongue is an insect-transmitted viral disease of sheep and some species of wild ruminants. Infection of lung microvascular endothelial cells (ECs) is central to the pathogenesis of bluetongue virus (BTV) infection of ruminants, but it is uncertain as to why cattle are resistant to BTV-induced microvascular injury and bluetongue disease. Thus, in order to better understand the pathogenesis of BTV infection of cattle, mRNAs encoding a variety of inflammatory mediators were quantitated by real-time polymerase chain reaction in primary bovine lung microvascular ECs (BLmVECs) exposed to BTV and/or EC-derived mediators. BTV infection of BLmVECs significantly increased the transcription of genes encoding interleukin-1 (IL-1), IL-6, IL-8, cyclooxygenase-2, and inducible nitric oxide synthase. Treatment of BLmVECs with EC-lysates that contained BTV as well as cytokines increased both the incidence of apoptosis and expression of cellular adhesion molecules, as compared to infection of BLmVECs with BTV alone. Thus, BTV infection caused activation of BLmVECs with production of inflammatory mediators that alter the mechanism of cell death of BLmVECs and exert potentially potent effects on blood coagulation. The activities of BTV-induced-EC-derived inflammatory mediators likely contribute to the resistance of cattle to BTV-induced microvascular injury and bluetongue disease.
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PMID:Bluetongue virus-induced activation of primary bovine lung microvascular endothelial cells. 1200 81

Pathogenic strains of Yersinia spp. inject a set of Yop effector proteins into eukaryotic cells by using a plasmid-encoded type III secretion system. In this study, we analyzed the inflammatory response of human umbilical vein endothelial cells (HUVECs) after infection with different Yersinia enterocolitica strains. We found that both expression of intercellular adhesion molecule 1 and release of the cytokines interleukin-6 (IL-6) and IL-8 by HUVECs are downregulated in a YopP-dependent way, demonstrating that YopP plays a major role in the inflammatory response of these cells. Infection of HUVECs with several low-virulence (biotype 2, 3, and 4) and high-virulence (biotype 1B) Y. enterocolitica strains showed that biotype 1B isolates are more efficient in inhibiting the inflammatory response than low-virulence Y. enterocolitica strains and that this effect depends on the time of contact. We extended the results of Ruckdeschel et al. and found that on the basis of the presence or absence of arginine-143 of YopP (K. Ruckdeschel, K. Richter, O. Mannel, and J. Heesemann, Infect. Immun. 69:7652-7662, 2001) all the Y. enterocolitica strains used fell into two groups, which correlate with the low- and high-virulence phenotypes. In addition, we found that high-virulence strains inject more YopP into the cytosol of eukaryotic target cells than do low-virulence strains.
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PMID:Effect of low- and high-virulence Yersinia enterocolitica strains on the inflammatory response of human umbilical vein endothelial cells. 1206 90

Bluetongue is an insect-transmitted disease of sheep and wild ruminants that is caused by bluetongue virus (BTV). Cattle are asymptomatic reservoir hosts of BTV. Infection of lung microvascular endothelial cells (ECs) is central to the pathogenesis of BTV infection of both sheep and cattle, but it is uncertain as to why sheep are highly susceptible to BTV-induced microvascular injury, whereas cattle are not. Thus, to better characterize the pathogenesis of bluetongue, the transcription of genes encoding a variety of vasoactive and inflammatory mediators was quantitated in primary ovine lung microvascular ECs (OLmVECs) exposed to BTV and/or inflammatory mediators. BTV infection of OLmVECs increased the transcription of genes encoding interleukin- (IL) 1 and IL-8, but less so IL-6, cyclooxygenase-2, and inducible nitric oxide synthase. In contrast, we previously have shown that transcription of genes encoding all of these same mediators is markedly increased in BTV-infected bovine lung microvascular ECs and that BTV-infected bovine ECs produce substantially greater quantities of prostacyclin than do sheep ECs. Thus, sheep and cattle were experimentally infected with BTV to further investigate the role of EC-derived vasoactive mediators in the pathogenesis of bluetongue. The ratio of thromboxane to prostacyclin increased during BTV infection of both sheep and cattle, but was significantly greater in sheep (P = 0.001). Increases in the ratio of thromboxane to prostacyclin, indicative of enhanced coagulation, coincided with the occurrence of clinical manifestations of bluetongue in BTV-infected sheep. The data suggest that inherent species-specific differences in the production and activities of EC-derived mediators contribute to the sensitivity of sheep to BTV-induced microvascular injury.
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PMID:The role of endothelial cell-derived inflammatory and vasoactive mediators in the pathogenesis of bluetongue. 1206 31

The responses of five lactating ewes to experimental mammary infection with Staphylococcus epidermidis were examined. Infection caused an intense but transient influx of neutrophils into milk, which peaked at 8 h and was accompanied by mild fever and mild leukopaenia in blood. No other signs of systemic infection were observed. Number of staphylococci in milk decreased logarithmically until 24 h, were absent from three ewes at 48 h and then increased in number or re-emerged in four of the five ewes at 72 or 144 h. At all times milk appeared grossly normal. Expression of the adhesion molecules CD11b and CD18 increased on neutrophils in milk at 24 h then tended to decline over subsequent days. The proportion of lymphocytes positive for CD4, CD8, WC1 and MHCII tended to decrease from 24 to 72 h then increased at 144 h. Cytokines in milk were measured by ELISA. IL-8 was elevated in infected glands at 2 h, peaked at 24 h and remained elevated until the final sampling at 144 h. IL-6 was transiently elevated at 4 and 8 h while IL-1beta remained elevated from 8 until 144 h. The results suggest that the intense early neutrophil infiltrate eliminated most but not all bacteria and a state of subclinical infection ensued. After 24 h , leukocyte numbers in milk declined while cytokines, especially IL-8 remained elevated, suggesting that sensitivity or responsiveness of gland to inflammatory signals decreased as infection progressed. This attenuation of the host defence response may have contributed to the failure of the gland to eliminate bacteria and may be an important feature of the development of chronic and subclinical mastitis.
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PMID:Immunological responses of the lactating ovine udder following experimental challenge with Staphylococcus epidermidis. 1220 51

Alveolar macrophages are likely the first cell type to encounter Mycobacterium tuberculosis in a pulmonary infection, resulting in the production of chemokines. In order to evaluate this response, alveolar macrophages harvested from nonvaccinated and Mycobacterium bovis BCG-vaccinated guinea pigs were infected in vitro with live M. tuberculosis H37Ra or H37Rv (multiplicity of infection, 1:1) or cultured with lipopolysaccharide (10 micro g/ml) for 3, 12, and 24 h. Interleukin-8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) mRNA expression was determined by real-time PCR. Culture supernatants were assayed for guinea pig IL-8 protein by using a human IL-8 enzyme-linked immunosorbent assay kit. Alveolar macrophages harvested from BCG-vaccinated guinea pigs produced significantly more mRNA and protein for IL-8 than alveolar macrophages harvested from nonvaccinated guinea pigs at 12 and 24 h poststimulation or postinfection. Infection with attenuated M. tuberculosis (H37Ra) stimulated alveolar macrophages isolated from BCG-vaccinated guinea pigs to produce significantly more IL-8 mRNA than did alveolar macrophages infected with a virulent strain (H37Rv) at 12 and 24 h postinfection. Significant MCP-1 mRNA production was also detected in stimulated or infected alveolar macrophages; however, prior vaccination did not significantly affect levels of MCP-1 mRNA. Alveolar macrophages isolated from BCG-vaccinated guinea pigs produced significantly more IL-8 mRNA and protein when stimulated for 24 h with heat-killed H37Ra, heat-killed H37Rv, and H37Rv cell wall, but not mannose-capped lipoarabinomannan (ManLAM), than did cells stimulated with media alone. These observations indicate that prior vaccination may alter very early events in the M. tuberculosis-infected lung.
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PMID:Mycobacterium bovis BCG vaccination augments interleukin-8 mRNA expression and protein production in guinea pig alveolar macrophages infected with Mycobacterium tuberculosis. 1222 72

Enterohaemorrhagic Escherichia coli O157:H7 (EHEC) is a gastrointestinal pathogen that is generally non-invasive for intestinal epithelial cells, yet causes acute intestinal inflammation, diarrhoea, haemorrhagic colitis and haemolytic uraemic syndrome. To study signal transduction pathways activated in human intestinal epithelial cells by EHEC, we took advantage of EHEC O157:H7 and isogenic mutants deficient in the major EHEC virulence factors, intimin (eae-) and Shiga toxin (stx-). Infection with wild-type EHEC activated p38 and ERK MAP kinases and the nuclear translocation of the transcription factor NF-kappaB. Downstream, this was accompanied by increased expression of mRNA and protein for the neutrophil chemoattractant IL-8. Isogenic eae- and stx- mutants also activated p38 and ERK MAP kinases, and NF-kappaB and stimulated increases in IL-8 protein secretion similar to those of wild-type EHEC. Further, inhibition of either p38, ERK or NF-kappaB activation abrogated the IL-8 response induced by wild-type EHEC and the mutants. Epithelial cell MAP kinase and NF-kappaB pathways leading to IL-8 secretion were also activated by isolated EHEC H7 flagellin, which was active when added to either the apical or basolateral surface of polarized human intestinal epithelial cells. We conclude that EHEC interacting with intestinal epithelial cells activates intracellular signalling pathways and an epithelial cell proinflammatory response independent of either Shiga toxin or intimin, two of the major known virulence factors of EHEC. The activation of proinflammatory signals in human colon epithelial cells in response to this non-invasive pathogen appears to depend to a significant extent on H7 flagellin.
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PMID:Role of EHEC O157:H7 virulence factors in the activation of intestinal epithelial cell NF-kappaB and MAP kinase pathways and the upregulated expression of interleukin 8. 1236 1

The responses of five lactating East Friesian milk ewes to experimental mammary infection with Staphylococcus epidermidis and of five control ewes were examined over a period of 10 weeks. Infection caused an influx of neutrophils into milk, the numbers of which started to rise 4 h post infection and peaked 24 h after infection. The initial response was accompanied by mild fever and mild leucopaenia in blood (8 h after infection). No other signs of systemic infection were observed. Milk appeared normal at all times, although the milk yield of infected ewes tended to decline. Staphylococci were absent in milk from four ewes at 2 d and at 3 d after infection, but re-emerged intermittently in four of five ewes at subsequent samplings. Cytokines in milk were measured by ELISA. IL-8 was elevated in infected glands at 2 h and peaked at 8 h. In the four ewes intermittently shedding bacteria, IL-8 remained elevated until the final sampling at 10 weeks. IL-1beta was transiently elevated at 1 d and 2 d and showed a pronounced peak in one sheep. Milk samples from this ewe were bacteriologically negative, somatic cell count (SCC) was within the normal range and the concentrations of IL-1beta, as well as IL-8, were similiar to the control group (n=5) from 1 week after infection until the final sampling. Histological examination revealed leucocytic infiltrates in the four glands remaining infected at the end of the experiment, and a high level of CD5+ lymphocytes in three ewes. The results suggest that the relationship between the initial neutrophil influx and the proinflammatory cytokines may be responsible for determining the course of infection. Subclinical mastitis due to coagulase-negative staphylococci leads to minor changes in milk yield and milk constituents.
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PMID:Dynamics of experimentally induced Staphylococcus epidermidis mastitis in East Friesian milk ewes. 1280 Aug 69

Numerous studies indicate that enteroviruses, such as the Coxsackievirus (CV) group, are linked to autoimmune diseases. Virus tropism and tissue access are modulated by vascular endothelial cells (ECs), mainly at the level of the microvasculature. Data on the permissiveness of ECs to CV are, however, scanty and derived from studies on large vessel ECs. To examine the susceptibility of microvascular ECs to infection of group B CV (CVB), human dermal microvascular ECs (HMEC-1) were infected with three CVB strains, and the immunological phenotype of the infected cells was analyzed. All CVB persistently infected the EC cultures without producing overt cytopathic effects. Infected ECs retained endothelial characteristics. Release of infectious particles in cell supernatants persisted for up to 3 mo of culture. Infection up-regulated expression of the adhesion molecules ICAM-1 and VCAM-1, with the highest values detected during the first 30 days of infection (p < 0.05 vs uninfected HMEC-1). CVB infection increased production of the proinflammatory cytokines, IL-6, IL-8, and TNF-alpha, which may account for the enhanced expression of adhesion molecules. Parallel infection of macrovascular HUVEC had less evident effects on induction of ICAM-1 and did not significantly increase expression of VCAM-1. Moreover, mononuclear cell adhesion to CVB-infected HMEC-1 monolayers was increased, compared with uninfected monolayers. These results provide evidence that small vessel ECs can harbor a persistent viral infection, resulting in quantitative modification of adhesion molecule expression, which may contribute to the selective recruitment of subsets of leukocytes during inflammatory immune responses. Furthermore, our data confirm that the behavior against a viral challenge of ECs in large vessels and microvessels may differ.
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PMID:Persistent infection of human microvascular endothelial cells by coxsackie B viruses induces increased expression of adhesion molecules. 1281 28

Infection and injury are frequently accompanied by hemolysis. Endothelial cells are direct targets of free Hb or its oxidative derivatives, including methemoglobin (MHb) and hemin. This study tested whether Hb or its derivatives alter chemokine (IL-8) and cytokine (IL-6) production and the membrane expression of cell adhesion molecule (E-selectin) in human umbilical vein endothelial cells (passages 2-4, HUVECs). E-selectin membrane content and IL-6 and IL-8 release were quantified by ELISA; cellular mRNA levels were determined by RT-PCR. MHb in vitro resulted in a dose (1-50 microM)- and time (2-16 h)-dependent increase in E-selectin membrane content and IL-6 and IL-8 release in HUVECs. The stimulatory effect of MHb (12 microM) on E-selectin membrane expression and IL-6 and IL-8 release was similar to that produced after treatment with TNF-alpha (5 ng/ml) and IL-1beta (0.25 ng/ml). In contrast, Hb or hemin had no effects. As expected, MHb, Hb, and hemin markedly induced heme oxygenase-1 expression in HUVECs. Haptoglobin, cytochalasin D, and actinomycin inhibited the MHb-induced responses, whereas zinc protoporphyrin IX (a heme oxygenase inhibitor) or desferroxamine (an iron chelator) did not inhibit MHb-induced responses. MHb also increased cellular mRNA levels of E-selectin, IL-6, and IL-8. MHb treatment activated cellular NF-kappaB and NF-kappaB inhibitors; N-acetyl cysteine, SN50, and caffeic acid phenylethyl ester inhibited the MHb-induced responses. These data indicate that MHb is a potent activator of endothelial cells through NF-kappaB-mediated upregulation of cell adhesion molecule expression and chemokine and cytokine production. MHb-induced endothelial cell activation may have clinical significance after infections, hemolysis, or methemoglobinemia.
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PMID:Methemoglobin is a potent activator of endothelial cells by stimulating IL-6 and IL-8 production and E-selectin membrane expression. 1283 37


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