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 the level of group IB secretory phospholipase A(2) (sPLA(2)-IB) has been reported to be up-regulated during inflammatory response, the role of sPLA(2)-IB on the regulation of inflammation and immune responses has not been fully elucidated. In this study, we found that sPLA(2)-IB stimulates the expression and secretion of CXCL8 without affecting other proinflammatory cytokines, such as IL-1beta or TNF alpha in human neutrophils. The induction of CXCL8 secretion by sPLA(2)-IB occurs at both the transcription and translational levels and correlates with activation of NF-kappaB. Moreover, the NF-kappaB inhibitors pyrrolidinedithiocarbamate, dexamethasone, or sulfasalazine were found to prevent CXCL8 production by sPLA(2)-IB in human neutrophils. In addition, the signaling events induced by sPLA(2)-IB included activation of the MAPK ERK and an increase in intracellular Ca(2+), which are both required for CXCL8 production. The exogenous addition of sPLA(2)-IB did not induce arachidonic acid release from human neutrophils, and the inactivation of sPLA(2)-IB by EGTA did not affect CXCL8 production by sPLA(2)-IB in human neutrophils. Taken together, we suggest that sPLA(2)-IB plays a role in the modulation of inflammatory and immune responses via the sPLA(2) receptor, by inducing CXCL8 in human neutrophils.
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PMID:Group IB secretory phospholipase A2 stimulates CXC chemokine ligand 8 production via ERK and NF-kappa B in human neutrophils. 1552 84

Electronegative low-density lipoprotein (LDL(-)) is a plasma-circulating LDL subfraction with proinflammatory properties that induces the production of chemokines in cultured endothelial cells. However, the specific mechanism of LDL(-)-mediated chemokine release is presently unknown. A characteristic feature of LDL(-) is an increased content of lysophosphatidylcholine (LPC) and non-esterified fatty acids (NEFA). The effect of increasing amounts of LPC and NEFA associated with LDL on the release of chemokines by endothelial cells was studied. Total LDL was subfractionated by anion-exchange chromatography in electropositive (LDL(+)) and LDL(-). LDL(-) contained two-fold more LPC and NEFA than LDL(+) and induced two- to four-fold more (p < 0.05) interleukin-8 (IL-8, 11.5 +/- 8.2 ng/10(5) cells) and monocyte chemotactic protein-1 (MCP-1, 10.8 +/- 3.8 ng/10(5) cells) release by human umbilical vein endothelial cells (HUVEC) than LDL(+) (IL-8: 3.4 +/- 1.5 ng/10(5) cells, MCP-1: 5.8 +/- 2.9 ng/10(5) cells). The content of LPC and NEFA in LDL(+) was increased by enzymatic treatment with secretory phospholipase A(2) (sPLA(2)) at 5 ng/mL or 20 ng/mL or by incubation with NEFA at 2 mmol/L. Modification of LDL(+) by both methods did not result in oxidative modification as demonstrated by the lack of change in antioxidants, conjugated dienes and malondialdehyde content. sPLA(2) treatment resulted in an increase in LPC and NEFA in LDL(+) which enhanced its ability to release IL-8 and MCP-1 by HUVEC in a concentration-dependent manner (sPLA(2)(5)-LDL; IL-8: 7.1 +/- 3.8ng/10(5) cells, MCP-1: 8.0 +/- 5.1 ng/10(5) cells; sPLA(2)(20)-LDL; IL-8: 20.8 +/- 11.2 ng/10(5) cells, MCP-1: 15.0 +/- 7.5 ng/10(5) cells). NEFA loading of LDL(+) also favored the release of IL-8 and MCP-1 (IL-8: 7.8 +/- 6.1 ng/10(5) cells, MCP-1: 8.4 +/- 2.7 ng/10(5) cells, p < 0.05 versus LDL(+)). These effects were observed when modified LDL(+) reached a content of LPC and/or NEFA similar that of LDL(-). These data indicate that non-oxidized polar lipids associated with LDL promote an inflammatory response in endothelial cells and suggest that increased NEFA and LPC could be involved in the inflammatory activity of LDL(-).
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PMID:Increased lysophosphatidylcholine and non-esterified fatty acid content in LDL induces chemokine release in endothelial cells. Relationship with electronegative LDL. 1553 Sep 3

Electronegative low-density lipoprotein (LDL(-)) is a modified subfraction of LDL present in plasma able to induce the release of interleukin 8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) by human umbilical vein endothelial cells (HUVEC). To ascertain whether further inflammation mediator release could be induced by LDL(-), a protein array system was used to measure 42 cytokines and related compounds. Native LDL and LDL(-) isolated from normolipemic subjects were incubated for 24 h with HUVEC and culture supernatants were used to measure inflammation mediator release. The protein array revealed that IL-6, granulocyte/monocyte colony-stimulating factor (GM-CSF) and growth-related oncogene (GRO) release were increased by cultured HUVEC in response to LDL(-). LDL(-) enhanced production of IL-6 (4-fold vs. LDL(+)), GM-CSF (4-fold), GRObeta (2-fold) and GROgamma (7-fold) was confirmed by ELISA. Time-course experiments revealed that IL-6 was released earlier than the other inflammation mediators, suggesting a first-wave cytokine action. However, the addition of IL-6 alone did not stimulate the production of IL-8, MCP-1 or GM-CSF. Moreover, IL-8, MCP-1 or GM-CSF alone did not promote the release of the other inflammatory molecules. Modification of LDL(+) by phospholipase A(2)-mediated lipolysis or by loading with non-esterified fatty acids (NEFA) reproduced the action of LDL(-), thereby suggesting the involvement of NEFA and/or lysophosphatidylcholine in the release of these molecules. Our results indicate that LDL(-) promotes a proinflammatory phenotype in endothelial cells through the production of cytokines, chemokines and growth factors.
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PMID:Wide proinflammatory effect of electronegative low-density lipoprotein on human endothelial cells assayed by a protein array. 1675 31

Lysophosphatidylcholine (LPC) is the major bioactive lipid component of oxidized LDL, thought to be responsible for many of the inflammatory effects of oxidized LDL described in both inflammatory and endothelial cells. Inflammation-induced transformation of vascular smooth muscle cells from a contractile phenotype to a proliferative/secretory phenotype is a hallmark of the vascular remodeling that is characteristic of atherogenesis; however, the role of LPC in this process has not been fully described. The present study tested the hypothesis that LPC is an inflammatory stimulus in coronary artery smooth muscle cells (CASMCs). In cultured human CASMCs, LPC stimulated time- and concentration-dependent release of arachidonic acid that was sensitive to phospholipase A2 and C inhibition. LPC stimulated the release of arachidonic acid metabolites leukotriene-B4 and 6-keto-prostaglandin F1alpha, within the same time course. LPC was also found to stimulate basic fibroblast growth factor release as well as stimulating the release of the cytokines GM-CSF, IL-6, and IL-8. Optimal stimulation of these signals was obtained via palmitic acid-substituted LPC species. Stimulation of arachidonic acid, inflammatory cytokines and growth factor release, implies that LPC might play a multifactorial role in the progression of atherosclerosis, by affecting inflammatory processes.
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PMID:Lysophosphatidylcholine induces inflammatory activation of human coronary artery smooth muscle cells. 1689 35

Acute pancreatitis in its severe form is complicated by multiple organ system dysfunction, most importantly by pulmonary complications which include hypoxia, acute respiratory distress syndrome, atelectasis, and pleural effusion. The pathogenesis of some of the above complications is attributed to the production of noxious cytokines. Clinically significant is the early onset of pleural effusion, which heralds a poor outcome of acute pancreatitis. The role of circulating trypsin, phospholipase A2, platelet activating factor, release of free fatty acids, chemoattractants such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, IL-8, fMet-leu-phe (a bacterial wall product), nitric oxide, substance P, and macrophage inhibitor factor is currently studied. The hope is that future management of acute pancreatitis with a better understanding of the pathogenesis of lung injury will be directed against the production of noxious cytokines.
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PMID:Pathophysiology of pulmonary complications of acute pancreatitis. 1713 69

To determine the genetic program mediating and maintaining the change from susceptibility to Crohn's disease (CD) to ongoing tissue destruction and loss of function, we utilized Affymetrix HG U95 AV2 Gene Chips and analyzed unpooled surgical CD colon specimens from adult patients. Using the patient as his own genetic filter we examined involved versus uninvolved adjacent areas, comparing results within one individual and then performing analysis comparing results between four individuals. Our results interrogated twice as many genes than the previous studies that used pooled unmatched specimens. We identified a limited set of nine genes upregulated in all four patients, and one gene (PTN) as downregulated. Several of the genes, including DEFA6, PAP, REG1A, REG1B, and phospholipase A2 had been implicated in previous studies, supporting their key role in CD. In 3 of 4 patients, 24 genes were upregulated in diseased areas, including DEFA5, IL-8, MMP-1, S100 calcium binding protein, and MGSA. Additional new candidate genes were identified, including DMT1, SERPINA1, GW112, and iNOS. The use of the unpooled samples allowed the detection of significant interindividual differences in expression of many other genes, supporting disease heterogeneity in CD. Results with select genes were confirmed with RT-PCR studies, as well as on biopsy samples from pediatric patients. We have determined a common profile of "late" CD, and also demonstrated the potential variability, suggesting possible differences in etiology, triggers, and the need for more individualized management. Additional studies to investigate protein expression of these candidate genes should be undertaken.
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PMID:Gene expression profiles of late colonic Crohn's disease. 1808 81

Multible organ failure (MOF) induced by mesenteric infarction is associated with a high mortality rate. This study reports eicosanoid and cytokine levels in the blood of three atherosclerotic patients who ultimately died from MOF induced by mesenteric infarction. High plasma levels of 6- keto-prostaglandin (PG) F(1alpha) (the stable metabolite of PGI(2)), interleukin (IL)-6 and IL-8 are observed whereas plasma tumour necrosis factor alpha (TNFalpha), TxB(2) (the stable metabolite of TxA(2)), PGE(2), leukotrienes (LT)B(4) and LTC(4), and whole blood platelet-activating factor levels are not different from values obtained in similarly severe atherosclerotic patients. This short report questioned the clinical involvement of TNFalpha during such a pathology where a persistent translocation of endotoxin has been observed through the gut endothelial barrier. Activation of phospholipase A(2) is suggested by the increase in the stable metabolite of PGI(2) and might be by itself or through lipidic metabolites, a major systemic stimulus of IL-6 and IL-8 production.
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PMID:Eicosanoid and cytokine levels in plasma of patients during mesenteric infarction. 1847 39

In the present study, we investigated the anti-inflammatory effects of a Kampo medicine Shosaikoto (TJ-9) using in vitro periodontal disease model, in which human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS) from Porphyromonas gingivalis (PgLPS) produce IL-6, IL-8 and prostaglandin E2 (PGE2). Treatment with PgLPS (10 ng/ml), TJ-9 (up to 1 mg/ml) and their combinations for 24 h did not affect the viability of HGFs. Moreover, TJ-9 did not alter LPS-induced IL-6 and IL-8 productions. However, TJ-9 significantly suppressed LPS-induced PGE2 production in a dose-dependent manner but TJ-9 alone did not affect basal PGE2 level. Western blotting demonstrated that TJ-9 decreased cyclooxygenase-2 (COX-2) expression in a dose-dependent manner but not phospholipase A2. Moreover, TJ-9 selectively and dose-dependently inhibited COX-2 activity. These results suggest that TJ-9 decreased PGE2 production by inhibition of both COX-2 expression and activity and that TJ-9 may be useful to improve gingival inflammation in periodontal disease.
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PMID:Preventive effects of a Kampo medicine, Shosaikoto, on inflammatory responses in LPS-treated human gingival fibroblasts. 1852 44

Inflammation plays a role in trans-10, cis-12 (10,12)-conjugated linoleic acid (CLA)-mediated delipidation and insulin resistance in adipocytes. Given the anti-inflammatory role of resveratrol (RSV), we hypothesized that RSV would attenuate inflammation and insulin resistance caused by 10,12 CLA in human adipocytes. RSV blocked 10,12 CLA induction of the inflammatory response by preventing activation of extracellular signal-related kinase and induction of inflammatory gene expression (i.e., IL-6, IL-8, IL-1beta) within 12 h. Similarly, RSV suppressed 10,12 CLA-mediated activation of the inflammatory prostaglandin pathway involving phospholipase A(2), cyclooxygenase-2, and PGF(2alpha). In addition, RSV attenuated 10,12 CLA increase of intracellular calcium and reactive oxygen species associated with cellular stress, and activation of stress-related proteins (i.e., activating transcription factor 3, JNK) within 12 h. 10,12 CLA-mediated insulin resistance and suppression of fatty acid uptake and triglyceride content were attenuated by RSV. Finally, 10,12 CLA-mediated decrease of peroxisome proliferator-activated receptor gamma (PPARgamma) protein levels and activation of a peroxisome proliferator response element (PPRE) reporter were prevented by RSV. RSV increased the basal activity of PPRE, suggesting that RSV increases PPARgamma activity. Collectively, these data demonstrate for the first time that RSV prevents 10,12 CLA-mediated insulin resistance and delipidation in human adipocytes by attenuating inflammation and cellular stress and increasing PPARgamma activity.
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PMID:Conjugated linoleic acid-mediated inflammation and insulin resistance in human adipocytes are attenuated by resveratrol. 1877 71

In the present study, we investigated the effects of a Kampo medicine Orento (TJ-120) on the production of prostaglandin E(2) (PGE(2)), interleukin (IL)-6 and IL-8 by human gingival fibroblasts (HGFs) treated with lipopolysaccharide from Porphyromonas gingivalis (PgLPS). HGFs proliferation was dose-dependently decreased with Orento at days 3 and 7. However, treatment with PgLPS (10 ng/ml), Orento (up to 1 mg/ml) and their combinations for 24 h did not affect the viability of HGFs. Orento suppressed PgLPS-induced PGE(2) production in a dose-dependent manner but did not alter basal PGE(2) level. In contrast, Orento did not alter PgLPS-induced IL-6 and IL-8 productions. These alterations by Orento were similar to those by a mitogen-activated protein kinase kinase (MAPKK/MEK) inhibitor, PD98059. A Orento showed no effect on cyclooxygenase (COX)-1 and COX-2 activities, and increased cytoplasmic phospholipase A(2) (cPLA(2)) expression and increased PgLPS-induced COX-2 expression. Orento suppressed PgLPS-induced mobility retardation of cPLA(2) band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels, that is cPLA(2) phosphorylation and its activation, while Orento alone did not alter cPLA(2) phosphorylation. Orento suppressed PgLPS-induced extracellular signal-regulated kinase (ERK) phosphorylation, which is known to lead to ERK activation and cPLA(2) phosphorylation. These results suggest that Orento decreased PGE(2) production by inhibition of cPLA(2) phosphorylation and its activation via inhibition of ERK phosphorylation, and also that Orento may be useful to improve gingival inflammation in periodontal disease.
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PMID:Preventive effects of a kampo medicine, orento on inflammatory responses in lipopolysaccharide treated human gingival fibroblasts. 2041 May 94


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