UNIPROT:P10145 - FACTA Search

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)

Using human endothelial cells, we define a mechanism that accounts for the induction of interleukin 8 (IL-8) by protein I/IIf, an adhesin from Streptococcus mutans serotype f. We report that protein I/IIf interactions with endothelial cells increased the tyrosine phosphorylation of three cellular components with relative mass of 145,000, 125,000 and 70,000 in endothelial cells. These proteins were identified as phospholipase Cgamma (PLCy), focal adhesion kinase (FAK) and paxillin after immunoprecipitation with monoclonal antibodies (mAbs) and immunoblotting with antiphosphotyrosine mAbs. These results suggested that beta1 integrins could be one of the components implicated in the modulin activity of protein I/IIf. By incubating protein I/IIf with either purified alpha5beta1 integrins or with alpha5beta1 integrins overexpressing CHO cells, we demonstrated that alpha5beta1 integrins act as cell receptors for protein I/IIf. We also showed that protein I/IIf interactions with alpha5beta1 integrins lead to IL-8 secretion. Using specific inhibitors, we demonstrated that protein I/IIf-induced IL-8 release involves mitogen-activated protein kinases (MAPKs), and that PLCgamma and PKC also seem to contribute to protein I/IIf stimulation. However, PI-3K activation is not involved in IL-8 release. Altogether, these results indicate that, after binding to alpha5beta1 integrins, protein I/IIf induces IL-8 release by activating the MAPKs signalling pathways.
...
PMID:Involvement of alpha5beta1 integrins in interleukin 8 production induced by oral viridans streptococcal protein I/IIf in cultured endothelial cells. 1120 49

Hepatitis C virus (HCV), a major cause of liver disease worldwide, is frequently resistant to the antiviral alpha interferon (IFN). The HCV nonstructural 5A (NS5A) protein has been implicated in HCV antiviral resistance in many studies. NS5A antagonizes the IFN antiviral response in vitro, and one mechanism is via inhibition of a key IFN-induced enzyme, the double-stranded-RNA-activated protein kinase (PKR). In the present study we determined if NS5A uses other strategies to subvert the IFN system. Expression of full-length NS5A proteins from patients who exhibited a complete response (FL-NS5A-CR) or were nonresponsive (FL-NS5A-NR) to IFN therapy in HeLa cells had no effect on IFN induction of IFN-stimulated gene factor 3 (ISGF-3). Expression of mutant NS5A proteins lacking 110 (NS5A-DeltaN110), 222 (NS5A-DeltaN222), and 334 amino-terminal amino acids and mutants lacking 117 and 230 carboxy-terminal amino acids also had no effect on ISGF-3 induction by IFN. Expression of FL-NS5A-CR and FL-NS5A-NR did not affect IFN-induced STAT-1 tyrosine phosphorylation or upregulation of PKR and major histocompatibility complex class I antigens. However, NS5A expression in human cells induced interleukin 8 (IL-8) mRNA and protein, and this effect correlated with inhibition of the antiviral effects of IFN in an in vitro bioassay. NS5A induced transcription of a reporter gene driven by the IL-8 promoter, and the first 133 bp of the IL-8 promoter made up the minimal domain required for NS5A transactivation. NS5A-DeltaN110 and NS5A-DeltaN222 stimulated the IL-8 promoter to higher levels than did the full-length NS5A protein, and this correlated with increased nuclear localization of the proteins. Additional mutagenesis of the IL-8 promoter suggested that NF-kappaB and AP-1 were important in NS5A-DeltaN222 transactivation in the presence of tumor necrosis factor alpha and that NF-IL-6 was inhibitory to this process. This study suggests that NS5A inhibits the antiviral actions of IFN by at least two mechanisms and provides the first evidence for a biological effect of the transcriptional activity of the NS5A protein. During HCV infection, viral proteins may induce chemokines that contribute to HCV antiviral resistance and pathogenesis.
...
PMID:Hepatitis C virus nonstructural 5A protein induces interleukin-8, leading to partial inhibition of the interferon-induced antiviral response. 1139 Jun 11

Exposure to ambient particulate matter (PM) in the Utah Valley has previously been associated with a variety of adverse health effects. To investigate intracellular signaling mechanisms for pulmonary responses to Utah Valley PM inhalation, human primary airway epithelial cells were exposed to aqueous extracts of PM collected from the year before (Y1), during (Y2), and after (Y3) the closure of a local steel mill located in the Utah Valley in this study. Transfection with kinase-deficient extracellular signal-regulated kinase (ERK) 1 constructs partially blocked Utah Valley PM-induced interleukin (IL)-8 promoter reporter activity. The mitogen-activated protein kinase/ERK kinase (MEK) activity inhibitor PD-98059 significantly abolished IL-8 released in response to Utah Valley PM, as did the epidermal growth factor (EGF) receptor kinase inhibitor AG-1478. Western blotting showed that Utah Valley PM induced phosphorylation of EGF receptor tyrosine, MEK1/2, and ERK1/2, which could be ablated with AG-1478 or PD-98059. For all findings, the potency of Utah Valley PM collected during Y2 was found to be lower relative to that of Y1 and Y3. These data demonstrate that Utah Valley PM can induce IL-8 expression partially through the activation of the EGF receptor signaling.
...
PMID:Activation of the EGF receptor signaling pathway in airway epithelial cells exposed to Utah Valley PM. 1143 24

Monocyte phagocytosis of pathogens or inflammatory debris leads to chemokine secretion and heralds the influx of leukocytes to the site of injury. Persistent chemokine secretion can lead to tissue damage. However, the mechanisms by which phagocytosis regulates chemokine synthesis remain poorly understood. As a first step, we have studied regulation of interleukin (IL) 8 gene expression after interaction with zymosan or latex. IL-8 secretion was consistently one- or twofold higher after incubation with zymosan than with latex. Nuclear factor (NF) kappaB translocation to the nucleus was induced by zymosan but not latex, indicating that its translocation is dependent on the nature of the phagocytic stimulus. NFkappaB activation coincided with IkappaBalpha degradation but had no effect on processing of NFkappaB1/p105, the precursor of the NFkappaB protein p50. The NFkappaB inhibitor gliotoxin abrogated zymosan-induced IL-8 synthesis in peripheral blood monocytes, further demonstrating that the induction of IL-8 mRNA by zymosan is NFkappaB dependent. SB203580 inhibition of the p38 mitogen-activated protein kinase (MAPK) pathway significantly decreased zymosan-induced IL-8 mRNA accumulation. Inhibitors of protein kinases A and C or tyrosine kinases had no significant effect on zymosan-induced IL-8 synthesis. These data indicate that p38 MAPK and NFkappaB are critical in controlling zymosan-induced IL-8 secretion.
...
PMID:Regulation of interleukin-8 gene expression after phagocytosis of zymosan by human monocytic cells. 1152 95

Endothelial cells play a pivotal role in the initiation and perpetuation of inflammation. C1q, the first component of the classical pathway of complement, is a potent stimulus leading to endothelial cell activation and cytokine production. The specific cellular mechanisms through which endothelial cells are stimulated by C1q are not known. We stimulated human umbilical vein endothelial cells (HUVEC) with either monomeric C1q or C1q-bearing immune complexes (C1q-IC) in the presence or absence of inhibitors of protein tyrosine kinases (PTK) or mitogen-activated protein kinases (MAPK). C1q-IC, but not monomeric C1q, induced IL-8 production in dose- and time-dependent fashion. R3, a cross-linking monoclonal IgM antibody against the 126 kD phagocytic C1q receptor (C1qR), also stimulated IL-8 production. IL-8 mRNA accumulation was detected by Northern blot analysis within 2 h of stimulation by the immune complexes and was enhanced by the addition of cycloheximide. Secretion of IL-8 by C1q-IC stimulated HUVEC was completely blocked by the PTK inhibitor, genistein or the MAPK inhibitor, UO126. These experiments demonstrate that C1q-IC-induced production of IL-8 in HUVEC is dependent upon the activation of PTK and MAPK. These findings also support a role for the phagocytic C1qR as an important activator of HUVEC by immune complexes.
...
PMID:C1q-bearing immune complexes induce IL-8 secretion in human umbilical vein endothelial cells (HUVEC) through protein tyrosine kinase- and mitogen-activated protein kinase-dependent mechanisms: evidence that the 126 kD phagocytic C1q receptor mediates immune complex activation of HUVEC. 1153 42

Sodium fluoride (NaF) has previously been reported to induce a strong IL-8 response in human epithelial lung cells (A549) via mechanisms that seem to involve the activation of G proteins. In the present study the signal pathways downstream of the G proteins have been examined. NaF induced a weak, but sustained increase in PKC activity. In contrast, the PKC activator TPA induced a relatively strong, but transient effect and augmented the NaF-induced PKC activity. TPA induced a marked IL-8 response compared to NaF. PDB, another PKC activator, was less effective, but augmented the IL-8 response to NaF. Pretreatment with TPA for 20 h, or the PKC inhibitor GF109203X for 1 h, abolished the basal and NaF-induced PKC activities and partially prevented the NaF-induced IL-8 response. Inhibition of the MAP kinase p38 by SB202190 partially reduced the IL-8 response to NaF, whereas a reduction in ERK activity by PD98059 led to an increased response. The NaF-induced IL-8 response was weakly augmented by the PKA stimulator forskolin and the G(i) inhibitor pertussis toxin. The PKA inhibitor H89 seemed to reduce the NaF-induced IL-8 response, but the measured effect was not statistically significant. BAPTA-AM, KN93 and W7, that inhibit Ca(2+)-linked effects, did not affect the IL-8 response. Furthermore, the tyrosine kinase inhibitor genestein, the PI-3 kinase inhibitor wortmannin and phosphatase inhibition were without effects. In conclusion, the data suggest that NaF-induced increase of IL-8 in A549 cells involved PKC- and p38-linked pathways, whereas an ERK-dependent pathway counteracted the response. Tyrosine kinases, Ca(2+)-linked pathways, PI-3 kinase, PKA and phosphatase inhibition seem to play no or minor roles in the fluoride-induced IL-8 response.
...
PMID:Mechanisms in fluoride-induced interleukin-8 synthesis in human lung epithelial cells. 1156 78

Neutrophil-dependent inflammation dependent on monosodium urate (MSU) crystal-induced IL-8 expression occurs in gout. MSU crystals activate phagocyte Src family tyrosine kinases and the serine/threonine kinase p70s6k. Thus, using monocytic THP-1 cells, we assessed the potential for Src family kinases and p70s6k to mediate MSU-induced IL-8 expression. MSU crystals induced phosphorylation of p70s6k and the Src kinases c-Src, Lyn, Hck, and Fyn. IL-8 expression was attenuated more by the Src kinase inhibitor PP1 than by the p70s6k inhibitor rapamycin. PP1 inhibited crystal-induced phosphorylation of ERK1/2 and IkappaBalpha and suppressed IkappaB kinase (IKK) activation and NF-kappaB binding to the IL-8 promoter, signals that mediate MSU-induced IL-8 expression. Transfection of the native Src inhibitor, C-terminal Src kinase (Csk), also suppressed crystal-induced c-Src, ERK1/2, and IkappaBalpha phosphorylation and IL-8 expression. We conclude that Src family tyrosine kinase signaling plays a significant role in MSU crystal-induced IL-8 expression via stimulation of ERK1/2 pathway and NF-kappaB activation.
...
PMID:Src family protein tyrosine kinase signaling mediates monosodium urate crystal-induced IL-8 expression by monocytic THP-1 cells. 1173 59

Residual oil fly ash (ROFA) is a constituent of pollutant particles that can produce lung injury and activate protein tyrosine phosphorylation cascade. In this study, we determined whether or not protein tyrosine phosphorylation caused lung injury, and if so, identified critical tyrosinephosphorylated proteins that mediated the injury. ROFA was instilled intratracheally into perfused rabbit lungs and injury responses, including increase in pulmonary artery pressure (Ppa), lung weight gain, as well as release of interleukin (IL)-1beta, IL-6, IL-8, and nitrite/nitrate were measured. ROFA increased Ppa and IL-1beta, but inhibited nitrite/nitrate accumulation. Vanadyl sulfate at concentration equivalent to the amount of vanadium detected in the perfusate of ROFA-treated lungs induced similar changes. ROFA enhanced tyrosine phosphorylation of lung proteins, including a 170-kDa protein, likely the epidermal growth factor (EGF) receptor as shown by immunoprecipitation. Pretreatment with genistein, a tyrosine kinase inhibitor, blocked the increase in Ppa and tyrosine phosphorylation of the 170-kDa protein. Intravascular administration of human EGF increased Ppa, and pretreatment with PD153035, an EGF receptor-specific tyrosine kinase inhibitor, attenuated ROFA-induced pulmonary vasoconstriction. These results indicate that tyrosine phosphorylation of EGF receptors in the lung, possibly as a result of inhibition of protein tyrosine phosphatases, mediates constriction of pulmonary vessels induced by ROFA.
...
PMID:Activation of EGF receptors mediates pulmonary vasoconstriction induced by residual oil fly ash. 1179 73

TFF-peptides (formerly P-domain peptides, trefoil factors) are typical secretory products of many mucous epithelia and are aberrantly secreted during chronic inflammatory diseases. They are known to enhance the migration of intestinal, corneal, and bronchial epithelial cells. Using the human bronchial epithelial cell line BEAS-2B as a model, it is shown here for the first time that TFF-peptides are capable of modulating the inflammatory response in vitro by regulating tumor necrosis factor-alpha-induced secretion of interleukin (IL)-6 and IL-8. In contrast, TFF2 itself does not change IL-6 and IL-8 secretion but triggers sustained activation of the extracellular signal-regulated kinases (ERK1/2) as well as phosphorylation of c-Jun N-terminal kinase (JNK). A complex differential regulation of tumor necrosis factor-alpha-induced IL-6 and IL-8 secretion by TFF2 is observed that involves signaling via protein kinase C and ERK1/2. Furthermore, the motogenic effect of TFF2 on BEAS-2B cells is analyzed using a modified Boyden chamber assay. This migratory effect is shown to be dependent not only on protein kinase C and ERK1/2 but also on the activation of the Src family of tyrosine kinases. Taken together, the data presented indicate an important physiological role of TFF-peptides during inflammatory conditions of mucous epithelia.
...
PMID:Protein kinase C and ERK activation are required for TFF-peptide-stimulated bronchial epithelial cell migration and tumor necrosis factor-alpha-induced interleukin-6 (IL-6) and IL-8 secretion. 1188 1

Periodontal disease is the major cause of adult tooth loss and is commonly characterized by a chronic inflammation caused by infection of oral bacteria. Porphyromonas gingivalis (P. gingivalis) is one of the suspected periodontopathic bacteria and is frequently isolated from the periodontal pockets of patients with chronic periodontal disease. The lipopolysaccharide (LPS) of P. gingivalis is a key factor in the development of periodontitis. Gingival fibroblasts, which are the major constituents of gingival connective tissue, may directly interact with bacteria and bacterial products, including LPS, in periodontitis lesions. It is suggested that gingival fibroblasts play an important role in the host responses to LPS in periodontal disease. P. gingivalis LPS enhances the production of inflammatory cytokines such as interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor alpha (TNF-alpha) in gingival fibroblasts. However, the receptor that binds with P. gingivalis LPS on gingival fibroblasts remained unknown for many years. Recently, it was demonstrated that P. gingivalis LPS binds to gingival fibroblasts. It was also found that gingival fibroblasts express CD14, Toll-like receptor 4 (TLR4), and myeloid differentiation primary response gene 88 (MyD88). P. gingivalis LPS treatment of gingival fibroblasts activates several intracellular proteins, including protein tyrosine kinases, and up-regulates the expression of monocyte chemoattractant protein-1 (MCP-1), extracellular signal-regulated kinase 1 (ERK1), and signal-regulated kinase 2 (ERK2), IL-1 receptor-associated kinase (IRAK), nuclear factor-kappaB (NF-kappaB), and activating protein-1 (AP-1). These results suggest that the binding of P. gingivalis LPS to CD14 and TLR4 on gingival fibroblasts activates various second-messenger systems. In this article, we review recent findings on the signaling pathways induced by the binding of P. gingivalis LPS to CD14 and Toll-like receptors (TLRs) in gingival fibroblasts.
...
PMID:Porphyromonas gingivalis lipopolysaccharide signaling in gingival fibroblasts-CD14 and Toll-like receptors. 1209 56

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