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)

Although homocysteine (Hcy) inhibits angiogenesis in vivo and in vitro, the mechanism(s) underlying this phenomenon are largely unclear. The hypothesis of the present work is that Hcy, while inducing the expression of antiangiogenic factors, inhibits the production of angiogenic factors. Mouse brain microvascular endothelial cells (MVEC) were cultured in the presence and absence of 20 microM Hcy for 24 hr in serum-free medium. Cell homogenates were incubated with Trans-Signal Angiogenesis Antibody Array containing antibodies to angiogenic activators (ANG, HGF, leptin, VEGF, IL-6, IL-8, PIGF, FGF-alpha/beta, TNF-alpha and TGF-alpha) and inhibitors (IFN-gamma, IL-12, IP-10, TIMP-1 and -2). The array membranes were scanned and normalized with positive controls. Angiogenesis and formation of capillaries were measured by culturing the MVEC in Matrigels. The capillary-like structures were identified by transmission microscopy. Hcy decreased the expression of leptin, IL-6, -8, PIGF, FGF-alpha and VEGF, while the levels of anti-angiogenic IL-12, IP-10 (chemokine) and TIMP-1 were increased by Hcy. The vascular tube-like structures by MVEC were decreased by increased Hcy. However, the addition of VEGF to Hcy-treated MVEC ameliorated the decreased Hcy-mediated capillary formation. The results suggest that Hcy inhibits angiogenesis, in part, by decreasing VEGF and increasing TIMP-1.
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PMID:Proteomic analysis of homocysteine inhibition of microvascular endothelial cell angiogenesis. 1570 57

The expression of TLRs on epithelial cells provides a first line of defense against invading pathogens. We investigated the regulated expression and function of TLR5 and TLR9 on human keratinocytes, because we found by immunohistochemistry that these TLRs are expressed in distinct layers of the epidermis. We found that TGF-alpha, a growth and differentiation factor that is present during wound healing and in psoriasis, increased the expression of both TLR5 and TLR9 on keratinocytes. In addition, TGF-alpha regulated the function of TLR5 and TLR9, because activation with their respective ligands enhanced the production of IL-8 and human beta-defensins. These findings provide evidence that TGF-alpha up-regulates TLR expression and function, augmenting host defense mechanisms at epithelial surfaces.
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PMID:TGF-alpha regulates TLR expression and function on epidermal keratinocytes. 1587 9

Among the gram-negative bacteria that cause mastitis, Escherichia coli are the most prevalent. The innate immune system provides initial protection against E. coli infection by detecting the presence of the foreign pathogens and by mounting an inflammatory response, the latter of which is mediated by cytokines such as IL-1beta, IL-8, and tumor necrosis factor (TNF)-alpha. Although changes in these cytokines during mastitis have been well-described, it is believed that other mediators moderate mammary gland inflammatory responses as well. The growth factors/cytokines transforming growth factor (TGF)-alpha, TGF-beta1, and TGF-beta2 are all expressed in the mammary gland and have been implicated in regulating mammary gland development. In other tissues, these growth factors/cytokines have been shown to moderate inflammation. The objective of the current study was to determine whether TGF-alpha, TGF-beta1, and TGF-beta2 milk concentrations were altered during the course of E. coli-induced mastitis. The contralateral quarters of 11 midlactating Holstein cows were challenged with either saline or 72 cfu of E. coli, and milk samples were collected. Basal milk levels of TGF-alpha, TGF-beta1, and TGF-beta2 were 98.81 +/- 22.69 pg/mL, 3.35 +/- 0.49 ng/mL, and 22.36 +/- 3.78 ng/mL, respectively. Analysis of whey samples derived from E. coli-infected quarters revealed an increase in milk levels of TGF-alpha within 16 h of challenge, and these increases persisted for an additional 56 h. Elevated TGF-beta1 and TGF-beta2 milk concentrations were detected in E. coli-infected quarters 32 h after challenge, and these elevations were sustained throughout the study. Because TGF-alpha, TGF-beta1, and TGF-beta2 have been implicated in mediating inflammatory processes, their induction during mastitis is consistent with a role for these molecules in mediating mammary gland host innate immune responses to infection.
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PMID:Increased milk levels of transforming growth factor-alpha, beta1, and beta2 during Escherichia coli-induced mastitis. 1590 28

Almost half of all clinical cases of mastitis are caused by Gram-negative bacteria. Among these bacteria, intramammary infection by Pseudomonas aeruginosa remains one of the most refractory to antibiotic therapy. The ability to recognize potentially harmful pathogens whether previously encountered or not, as well as the induction of an initial pro-inflammatory response to these pathogens, are critical components of host innate immunity. Although the innate immune response to another Gram-negative mastitis-causing pathogen, Escherichia coli, has been well-characterized, little is known about the response to other Gram-negative bacteria, including P. aeruginosa. The objective of the current study was to characterize the systemic and localized bovine innate immune response to intramammary infection with P. aeruginosa. The contralateral quarters of ten mid-lactating Holstein cows were challenged with either saline or P. aeruginosa. Following the establishment of infection, milk samples were collected and assayed for changes in cytokine and growth factor concentrations, complement activation, and changes in the levels of soluble CD14 (sCD14) and lipopolysaccharide (LPS)-binding protein (LBP), two accessory molecules involved in host recognition of Gram-negative bacteria. Initial increases in milk somatic cell counts were evident within 12h of experimental challenge and remained elevated for >or=3 weeks. Increased permeability of the mammary gland vasculature, as evidenced by elevated milk levels of BSA, was initially observed 20 h post-infection and persisted for 2 weeks. Within 32 h of challenge, increased levels of IL-8, TNF-alpha, IL-10, and IL-12 were detected, however, the elevated levels of these cytokines were not sustained for longer than a 24h period. In contrast, elevations in IL-1beta, IFN-gamma, TGF-alpha, TGF-beta1, TGF-beta2, sCD14, LBP, and activated complement factor 5 (C5a) were sustained for periods of >48 h. Systemic changes were characterized by elevated body temperature, induction of the acute phase protein synthesis of serum amyloid A and LBP, and a transient decrease in circulating neutrophils and lymphocytes. Together, these data demonstrate the capability of the mammary gland to mount a robust innate immune response to P. aeruginosa that is characterized by the induction of pro-inflammatory cytokines, complement activation, and increased levels of accessory molecules involved in Gram-negative bacterial recognition.
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PMID:The bovine innate immune response during experimentally-induced Pseudomonas aeruginosa mastitis. 1597 Mar 35

In contrast to other mastitis pathogens, the host response evoked during Staphylococcus aureus intramammary infection is marked by the absence of the induction of critical cytokines, including IL-8 and TNF-alpha, which have established roles in mediating host innate immunity. The elucidation of changes in the expression of other mediators with the potential to regulate mammary inflammatory responses to S. aureus remains lacking. Transforming growth factor (TGF)-alpha, TGF-beta1, and TGF-beta2 are cytokines that regulate mammary gland development. Because these cytokines also have a demonstrated role in mediating inflammation, the objective of the current study was to determine whether S. aureus intramammary infection influences their expression. Ten cows were challenged with S. aureus and milk samples collected. Increases in milk levels of TGF-alpha were evident within 32h of infection and persisted for 16h. Increases in TGF-beta1 and TGF-beta2 levels were detected within 40h of S. aureus infection and persisted through the end of the study. Thus, in contrast to IL-8 and TNF-alpha, S. aureus elicits host production of TGF-alpha, TGF-beta1, and TGF-beta2. This finding may suggest a role for these cytokines in mediating mammary gland host innate immune responses to S. aureus.
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PMID:Staphylococcus aureus intramammary infection elicits increased production of transforming growth factor-alpha, beta1, and beta2. 1675 Feb 72

Airways function as an innate immune organ against airborne bacteria that are inhaled and deposited in airways. One of the mechanisms of host defense is to recruit neutrophils into airways to clear the invaders. Airway epithelial cells produce neutrophil chemoattractant interleukin (IL)-8 in response to invading bacteria. In this study we show a signaling pathway on the plasma surface of human airway epithelial NCI-H292 cells that regulate IL-8 production in response to a model inflammatory stimulus, phorbol 12-myristate 13-acetate, and a pathophysiological stimulus, gram-negative bacterial lipopolysaccharide. First, we show that EGF receptor (EGFR) and MAP kinase ERK1/2 are involved in IL-8 expression by these stimuli. Second, we show that EGFR ligand transforming growth factor (TGF)-alpha mediates IL-8 production. Third, we show that tumor necrosis factor-alpha-converting enzyme (TACE) is required for IL-8 production by cleaving EGFR proligand proTGF-alpha into soluble TGF-alpha, activating EGFR. Last, we show that dual oxidase 1 (Duox1), a homolog of NADPH oxidase in airways, mediates TACE activation and IL-8 expression via generation of reactive oxygen species. In summary, we describe a signaling pathway, Duox1-TACE-TGF-alpha-EGFR, on the surface of airway epithelial (NCI-H292) cells that mediates airway epithelial defense against bacterial infection by producing IL-8. This pathway, which also regulates mucin production in human airways, provides mechanisms for killing foreign organisms and for their clearance.
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PMID:Regulation of interleukin-8 via an airway epithelial signaling cascade. 1722 Mar 69

While acute changes in systemic pro-/antiinflammatory cytokines occur with exercise, individual kinetics during and following exercise remain unclear; particularly, information is scarce regarding children. This study investigated the exercise-induced kinetic profiles of major pro-/anti-inflammatory mediators in 21 healthy children (13.9 +/- 0.8 yr, 7 M/14 F). Exercise was 30 min of intermittent cycling at approximately 80% VO2max. Multiple blood samples were drawn at baseline, during, and following exercise for cytokines assay. IL-1alpha, IL-6, IL-17, IL-8, IP-10, MIP-1alpha, and MIP-1beta initially decreased (nadir: 14-19 min into exercise) and subsequently exceeded baseline levels (peaks: 20-24 min into exercise). TNF-alpha, IL-12p70, IL-1RA, IL-4, EGF, TGF-alpha, GM-CSF, Eotaxin, and MCP-1 were moderately and persistently decreased throughout. VEGF was unchanged; sCD40L was elevated during exercise and recovery. Our results indicate that key immunomodulators display non-linear, biphasic kinetic profiles in response to exercise, suggesting that detection of exercise-induced changes over baseline may depend on exercise duration and sampling timing.
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PMID:Kinetic profiles of 18 systemic pro- and anti-inflammatory mediators during and following exercise in children. 1834 Oct 89

Toll-like receptors (TLRs) are critical for the recognition of inhaled pathogens that deposit on the airway epithelial surface. The epithelial response to pathogens includes signaling cascades that activate the EGF receptor (EGFR). We hypothesized that TLRs communicate with EGFR via epithelial signaling to produce certain innate immune responses. Airway epithelium expresses the highest levels of TLR2, TLR3, TLR5, and TLR6, and here we found that ligands for these TLRs increased IL-8 and VEGF production in normal human bronchial epithelial cells. These effects were prevented by treatment with a selective inhibitor of EGFR phosphorylation (AG-1478), a metalloprotease (MP) inhibitor, a reactive oxygen species (ROS) scavenger, and an NADPH oxidase inhibitor. In an airway epithelial cell line (NCI-H292), TNF-alpha-converting enzyme (TACE) small interfering RNA (siRNA) was used to confirm that TACE is the MP involved in TLR ligand-induced IL-8 and VEGF production. We show that transforming growth factor (TGF)-alpha is the EGFR ligand in this signaling cascade by using TGF-alpha neutralizing antibody and by showing that epithelial production of TGF-alpha occurs in response to TLR ligands. Dual oxidase 1 (Duox1) siRNA was used to confirm that Duox1 is the NADPH oxidase involved in TLR ligand-induced IL-8 and VEGF production. We conclude that multiple TLR ligands induce airway epithelial cell production of IL-8 and VEGF via a Duox1--> ROS--> TACE--> TGF-alpha--> EGFR phosphorylation pathway. These results show for the first time that multiple TLRs in airway epithelial cells produce innate immune responses by activating EGFR via an epithelial cell signaling cascade.
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PMID:Multiple TLRs activate EGFR via a signaling cascade to produce innate immune responses in airway epithelium. 1837 43

Acute kidney injury (AKI) is a common disorder associated with high morbidity and mortality rates. Ischemia is the leading cause of AKI. This is a pilot study investigating the ability of multiple urinary cytokines to predict renal functional outcome and mortality in patients with ischemic AKI. Urine samples were obtained from 45 subjects with ischemic AKI on the day of renal consultation and 3 days later. The urinary concentrations of interleukin (IL)-1beta, IL-6, IL-8, monocyte chemotactic protein (MCP)-1, interferon-inducible protein (IP)-10, regulated on activation, normal T-expressed and secreted (RANTES), transforming growth factor (TGF)-alpha, vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) were measured simultaneously using a microsphere-based immunofluorescence assay. Urinary cytokine levels (pg/mg urine creatinine), which predict renal functional recovery or no recovery the next day and 7 days and 3 months later, were identified. Increased urinary IP-10 and IL-8 predicted no renal functional recovery the next day. Increased urinary IP-10 and VEGF predicted no renal recovery by 7 days. Increased urinary IP-10 and VEGF predicted no renal recovery by 4 days, whereas increased urinary EGF predicted renal functional recovery at that time. Increased urinary IL-8, MCP-1, IP-10, RANTES, EGF, and VEGF predicted patient's death within 3 months. Our findings suggest that urinary IP-10, IL-8, VEGF, TGF-alpha, and EGF may predict renal functional outcome at various times along the course of ischemic AKI and that urinary IL-8, MCP-1, IP-10, RANTES, EGF, and VEGF may predict mortality of the patients within 3 months.
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PMID:Simultaneous monitoring of multiple urinary cytokines may predict renal and patient outcome in ischemic AKI. 2054 Jun 38

It is now possible to identify several key factors that determine biological characteristics of squamous cell cancer of the head and neck: genes p53, p16, cyclin D1, P13-K/Akt connected with metastasis proteins (proteases, proteins mesenchymal cells, cell adhesion molecules chemokines), angiogenesis factors (VEGF, PDGF, FGF, TGF-alpha and TGF-beta), IL-8; epidermal growth factor receptors. An important role of tumor cells plays microenvironment. Of course the above mentioned is only a small part of the factors that determine the livelihoods and the activity of cancer cells. All of these factors are potential predictors of the effectiveness of radiation and chemoradiation treatment and actively studied in recent decades.
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PMID:[Prognostic value of clinical and morphological characteristics in radiation and combined treatment for tongue cancer]. 2601 52


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