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 response to bacterial infection, airway epithelium releases inflammatory mediators including cytokines and chemokines that lead to immune cell efflux and could stimulate the adaptive T cell immune response. The aim of our study was to analyze, in a double chamber culture, the chemokine changes in response to Staphylococcus aureus and their consequences for T cells. Our data show that S. aureus stimulates basolateral and apical release of IL-8 and eotaxin by airway epithelial cells. We also observed increased chemokine receptor expression on CD8+ and CD4+ T cells and enhanced chemotaxis of CD4+ T cells toward apical supernatant. Our data strongly suggest that S. aureus interaction with airway epithelium contributes to specific migration of T cells to inflamed sites.
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PMID:T cell chemotaxis and chemokine release after Staphylococcus aureus interaction with polarized airway epithelium. 1628 62

Nicotine, the major addictive component of tobacco, is an immunomodulator that impacts on many cells, including immune cells involved in inflammatory processes. Nicotine also induces oxidative damage to the vascular endothelium and accentuates lipid peroxidation, resulting in vascular cell dysfunction. Furthermore, vascular endothelial cells produce growth factors, such as cytokines and chemokines capable of stimulating and recruiting immune cells to atheromatous lesions. In addition, bacterial products including lipopolysaccharides (LPS), a major component of Gram negative bacterial cell walls, activate gene expression resulting in inflammatory cytokine production causing further damage to the vasculature. In the present study, the combined effects of nicotine and bacterial LPS on the expression of IL-6, IL-8, GRO-alpha and MCP-1 in cell lines of human coronary artery endothelial cells (HCAEC) and pulmonary monocytes (THP-1) were examined by quantitative real-time PCR and ELISA. Results showed that nicotine suppressed the LPS induced production of IL-6 and IL-8 in both cell lines. Since cytokines which alter homeostasis of both vascular endothelial and immune cells are critical for the atherogenic process, further studies are warranted to examine in detail the role of nicotine in terms of effects on inflammatory reactions, including those induced by bacterial infection.
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PMID:Nicotine modulation of cytokine induction by LPS-stimulated human monocytes and coronary artery endothelial cells. 1633 10

LL-37 is a human cationic host defense peptide that is present in the specific granules of neutrophils, produced by epithelial cells from a variety of tissues, and is upregulated during inflammation, infection, and injury. It has been proposed to have a variety of antimicrobial functions, including both direct antimicrobial activity and immunomodulatory functions. Using the TUNEL assay it was demonstrated that LL-37 induced apoptosis in vitro in the A549 human lung and 16 HBE4o- human airway epithelial cell lines, and in vivo in the murine airway. Peptide-induced apoptosis in vitro involved the activation of caspase pathways and was substantially inhibited by an inhibitor of caspase 3. Apoptosis was also inhibited by human serum, but not fetal bovine serum. Similarly, human but not fetal bovine serum inhibited the cellular internalization of LL-37 and the production of IL-8 in response to LL-37 treatment of epithelial cells. The protective effects of human serum were also observed with high-density lipoproteins but not by the core peptide apolipoprotein A1, providing one possible mechanism of human serum inhibition of apoptosis. We propose that LL-37-induced apoptosis of epithelial cells at low serum tissue sites may have a protective role against bacterial infection.
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PMID:Apoptosis of airway epithelial cells: human serum sensitive induction by the cathelicidin LL-37. 1634

The means by which airway epithelial cells sense a bacterial infection and which intracellular signalling pathways are activated upon infection are poorly understood. A549 cells and human primary airway cells (NHBE) were used to investigate the response to infection with Klebsiella pneumoniae. Infection of A549 and NHBE with K. pneumoniae 52K10, a capsule polysaccharide (CPS) mutant, increased the surface levels of ICAM-1 and caused the release of IL-8. By contrast, the wild-type strain did not elicit these responses. Consistent with a functional role for these responses, there was a correlation between ICAM-1 levels and the number of adherent leukocytes on the epithelial cell surface. In addition, treatment of neutrophils with IL-8 enhanced their ability to kill K. pneumoniae. Strain 52K10 was internalized by A549 cells more efficiently than the wild-type, and when infections with 52K10 were performed in the presence of cytochalasin D the inflammatory response was abrogated. These findings suggest that cellular activation is mediated by bacterial internalization and that CPS prevents the activation through the blockage of bacterial adhesion and uptake. Collectively, the results indicate that bacterial internalization by airway epithelial cells could be the triggering signal for the activation of the innate immune system of the airway. Infection of A549 cells by 52K10 was shown to trigger the nuclear translocation of NF-kappaB. Evidence is presented showing that 52K10 activated IL-8 production through Toll-like receptor (TLR) 2 and TLR4 pathways and that A549 cells could use soluble CD14 as TLR co-receptor.
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PMID:The uptake of a Klebsiella pneumoniae capsule polysaccharide mutant triggers an inflammatory response by human airway epithelial cells. 1643 43

Mastitis, a mammary gland inflammation in response to bacterial infection, is a major problem in the dairy industry. We found that cows susceptible to mastitis have a three-base insertion in a glycine-coding stretch of the gene for forebrain embryonic zinc finger-like (FEZL), a transcription factor with a role in neuronal development. Mastitis induces FEZL expression in mammary glands, and induced FEZL promotes expression of the axon-attracting molecule semaphorin 5A (SEMA5A) through a GCAG sequence. FEZL also induces SEMA5A expression in susceptible cattle but at a lower level than in resistant cattle. Enhanced SEMA5A induces expression of at least nine genes related to the host's immune response, including TNF-alpha and IL-8. We propose that susceptibility to mastitis results from an impaired immune response due to the lower transcription activity of susceptible FEZL. Our results provide an avenue to select for genetic improvement of resistance to mastitis and suggest that the FEZL-SEMA5A pathway might control both neuronal development and innate immunity.
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PMID:Evidence that bovine forebrain embryonic zinc finger-like gene influences immune response associated with mastitis resistance. 1661 27

Whereas adaptive immunity has been extensively studied, very little is known about the innate immunity of the host to HTLV-I infection. HTLV-I-infected ATL patients have pronounced immunodeficiency associated with frequent opportunistic infections, and in these patients, concurrent infections with bacteria and/or parasites are known to increase risks of progression to ATL. The Toll-like receptor-4 (TLR4) activation in response to bacterial infection is essential for dendritic cell maturation and links the innate and adaptive immune responses. Recent reports indicate that TLR4 is targeted by viruses such as RSV, HCV, and MMTV. Here we report that HTLV-I has also evolved a protein that interferes with TLR4 signaling; p30 interacts with and inhibits the DNA binding and transcription activity of PU.1 resulting in the down-regulation of the TLR4 expression from the cell surface. Expression of p30 hampers the release of pro-inflammatory cytokines MCP-1, TNF-alpha, and IL-8 and stimulates release of anti-inflammatory IL-10 following stimulation of TLR4 in human macrophage. Finally, we found that p30 increases phosphorylation and inactivation of GSK3-beta a key step for IL-10 production. Our study suggests a novel function of p30, which may instigate immune tolerance by reducing activation of adaptive immunity in ATL patients.
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PMID:The HTLV-I p30 interferes with TLR4 signaling and modulates the release of pro- and anti-inflammatory cytokines from human macrophages. 1678 40

The maintenance of pregnancy depends on the nature and magnitude of the immune responses induced within the placenta. An elevated proinflammatory response in the intervillous space (IVS) is associated with adverse pregnancy outcomes. It is becoming more apparent that the syncytiotrophoblast (ST) cells, which are in direct contact with maternal blood, are capable of contributing to the local immune environment in response to maternal hematogenous infections or exposure to proinflammatory stimuli. In this study, we investigated mechanisms by which ST might recruit maternal immune effectors to the IVS in response to bacterial infections. To assess this, primary trophoblasts were isolated from fresh term placentas and stimulated with lipopolysaccharide (LPS). LPS induced time-dependent expression and secretion of IL-8, macrophage inflammatory protein (MIP)-1alpha and MIP-1beta from ST cells and an upregulation of ICAM-1. The stimulation also resulted in the activation of ERK1/2 mitogen-activated protein kinase (MAPK) but not p38 or JNK1/2. Inhibition of ERK1/2 lead to a reduction in the secretion of MIP-1beta and IL-8 suggesting that their production is at least partly dependent on ERK1/2 activation. Results from this study reveal a potential mechanism by which differentiated ST cells modulate the local maternal immune responses during an intrauterine bacterial infection. Such responses could contribute to the clearance of the infection but also pathological features observed in intrauterine infections of the placenta.
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PMID:LPS induces secretion of chemokines by human syncytiotrophoblast cells in a MAPK-dependent manner. 1687 Feb 63

The Serratia marcescens-derived protease serralysin is considered to play an important role in the pathogenesis of infection. Protease-activated receptor 2 (PAR-2) is activated by trypsin and also several other trypsin-like serine proteases, leading to the modulation of inflammatory and immune responses. However, little is known about the activation of PAR-2 by bacterial proteases and its roles in bacterial infection. In this study, we investigated whether S. marcescens serralysin activates host inflammatory responses through PAR-2. Our results demonstrated that serralysin induces interleukin-6 (IL-6) and IL-8 mRNA expression in a human lung squamous cell carcinoma, EBC-l cells. In addition, serralysin activated activator protein 1 (AP-1)-, CCAAT/enhancer-binding protein (C/EBP)-, and nuclear factor-kappaB (NF-kappaB)-driven promoters in EBC-1 cells. An electrophoretic mobility shift assay showed that serralysin activates the binding of AP-1, C/EBPbeta, and NF-kappaB in the cells. Inactivation of serralysin resulted in the failure of transactivation of AP-1-, C/EBP-, and NF-kappaB-driven promoters in the cells. Furthermore, serralysin activated AP-1-, C/EBP-, and NF-kappaB-driven promoters via PAR-2 in HeLa cells. PAR-2 antagonist peptides decreased serralysin-induced transactivation of AP-1-, C/EBP-, and NF-kappaB-driven promoters in EBC-1 cells. Considered together, these results suggest that serralysin requires PAR-2 to activate the critical transcription factors AP-1, C/EBPbeta, and NF-kappaB for host inflammatory responses.
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PMID:Serratia marcescens serralysin induces inflammatory responses through protease-activated receptor 2. 1704 6

Recent reports have shown that Staphylococcus aureus infection increases the expression of cytokines and cell adhesion molecules in endothelial cells and enhances leucocyte migration, thereby resulting in bacterial elimination. In this study, we analysed the production of the chemokine interleukin (IL)-8 in human umbilical vein endothelial cells (HUVEC) infected with several S. aureus strains by using reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. We found that the avirulent strains (00-51 and 00-62) increased IL-8 production but the virulent strains (A17 and A151) decreased it at both the mRNA and protein levels. We considered that the inhibition of IL-8 production depended on certain inhibitory factor(s) secreted by bacteria. This was because S. aureus also abolished IL-8 expression in HUVEC treated with cytochalasin D, and the addition of culture supernatants of strains A17 and A151 decreased IL-8 production in HUVEC. This factor(s) in the bacterial culture supernatant inhibited both basal and tumour necrosis factor (TNF)-alpha-induced IL-8 production. In contrast, no inhibitory effect was observed on monocyte chemotactic protein-1 (MCP-1) production. These results indicate that S. aureus can down-regulate IL-8 release in endothelial cells through the secretion of inhibitory factor(s), and this may result in decreased neutrophil recruitment, thus interfering with the host immune response to bacterial infection.
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PMID:Inhibition of interleukin-8 production in human endothelial cells by Staphylococcus aureus supernatant. 1717 74

The impaired infection control related to the functional immaturity of the neonatal immune system is an important cause of infection in preterm newborns. We previously reported that constitutive Toll-like receptor (TLR) 4 expression and cytokine secretion on lipopolysaccharide (LPS) stimulation increases with gestational age. Here, we analyzed constitutive monocyte TLR2 expression and evaluated the expression profiles of the proximal downstream adapter molecule myeloid differentiation factor 88 (MyD88). We further investigated activation of protein kinases p38 and extracellular regulated kinsase (ERK) 1/2 in CD14 monocytes after ex vivo stimulation with bacterial TLR ligands (LPS and lipoteichoic acid [LTA]). The functional outcome of the stimulation was determined by cytokine secretion. Monocytes from 31 preterm newborns (<30 weeks of gestation, n=16; 30-37 weeks of gestation, n=15), 10 term newborns, and 12 adults were investigated. In contrast to TLR4 expression, TLR2 levels did not differ between age groups. However, MyD88 levels were significantly lower in preterm newborns. Activation of p38 and ERK1/2 was impaired in all newborn age groups after stimulation with TLR-specific ligands. Accordingly, after LTA stimulation, the levels of interleukin (IL)-1 beta , IL-6, and IL-8 cytokine production were substantially lower (P<.001) in preterm newborns than in adults. The reduced functional response to bacterial cell wall components appears to be part of the functional immaturity of the neonatal immune system and might predispose premature newborns to bacterial infection.
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PMID:Immaturity of infection control in preterm and term newborns is associated with impaired toll-like receptor signaling. 1719 Nov 75


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