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)

GRO-alpha, GRO-beta and GRO-gamma are closely related peptides that stimulate growth of tumor cells and activate leukocytes in acute inflammatory reactions. In order to study the biology of GRO peptides in the lungs of experimental animals, we have developed and characterized a sensitive and specific immunoassay for rabbit GRO, and used this assay to measure GRO in rabbit lung fluids and plasma. GRO was cloned from a rabbit cDNA library and expressed in Escherichia coli. Specific goat polyclonal antibodies were used to create an antigen-capture immunoassay. The assay is sensitive to approximately 30 pg/ml GRO and does not crossreact with rabbit IL-8 or MCP-1, or human GRO. The assay accurately measures GRO in rabbit bronchoalveolar lavage fluid, plasma and serum. Rabbit erythrocytes bind little GRO and do not interfere with the detection of GRO in lung fluids. Circulating GRO was detected in the plasma of 4 of 6 pathogen-free rabbits, but the function of circulating GRO in normal animals is uncertain. This immunoassay will facilitate the study of the biology of GRO in rabbits with acute and chronic inflammation in the lungs and other tissues.
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PMID:A sensitive immunoassay to detect the alpha-chemokine GRO in rabbit blood and lung fluids. 929 94

Interleukin-8 possesses chemotactic-activating properties toward neutrophils, and may contribute to the pathogenesis of middle ear inflammation. GRO/CINC-1 is a rat chemokine with structural and functional homology to human interleukin-8, the induction and regulation of which in the middle ear cavity in vivo remains to be established. The production of GRO/CINC-1 in middle ear lavage and gene expression in the middle mucosa was investigated using topical inoculation with lipopolysaccharide (LPS) in the rat in vivo model. GRO/CINC-1 in middle ear lavage showed time- and dose-dependent production under LPS stimulation. The peak of the GRO/CINC-1 production was reached by 4 h after LPS 1 h exposure, whereas the level of production subsequently returned to the level without LPS stimulation at 8 h after LPS stimulation. The topical corticosteroid perfusion in the middle ear after LPS stimulation significantly reduced the production of GRO/CINC-1 in the middle ear cavity compared with that without corticosteroid. At the time of peak production, the expression of GRO/CINC-1 mRNA, evaluated using the polymerase chain reaction, was considerable in the middle ear mucosa. This investigation of the characteristics of interleukin-8-like cytokine in the middle ear cavity using a rat in vivo model has extended the functional concept of chemokines at the initial stage in otitis media.
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PMID:In vivo induction and regulation of interleukin-8-like chemokine GRO/CINC-1 in rat middle ear. 934 69

Chemokines are a family of low-molecular-weight proinflammatory cytokines that have leukocyte chemotactic and activating properties. Chemokine protein and mRNA are increased in the gastric mucosa of Helicobacter pylori infection and they are considered to regulate migration of leukocyte populations. The increase of C-X-C chemokines (e.g. IL-8, GRO-alpha) which effect primarily neutrophils is significantly associated with gastric polymorphonuclear cell activity suggesting that these chemokines play a primary role in active gastritis induced by H. pylori infection. In vitro enhanced epithelial chemokine responses are induced by cagA positive strains which have been clinically associated with more severe clinical outcome. Infection with cagA-positive H. pylori strains associates in vivo specifically with a C-X-C profile and enhanced polymorphonuclear infiltration in the gastric mucosa. Whilst infection with H. pylori, especially cag positive strains, is associated with more severe disease, genetic variability in host chemokine responses may also contribute to disease outcome.
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PMID:Mucosal chemokines in Helicobacter pylori infection. 937 14

CXCR2 is a seven-transmembrane receptor that transduces intracellular signals in response to the chemokines IL-8, MGSA/GRO, and other ELR motif-containing CXC chemokines by coupling to heterotrimeric GTP-binding proteins. In this study, we have mutated two putative G protein-coupling regions of CXCR2 and characterized the effects of these mutations on ligand-activated signal transductions: aspartic acid 89 in the second transmembrane domain and the HRAMR sequence (BBXXB motif, found in the third intracellular loop where B indicates a basic amino acid and X represents any amino acid). The Asp89 was replaced by either asparagine (D89N) or glutamic acid (D89E). For the BBXXB motif, the first two basic amino acids were mutated to two neutral isoleucines (HR-II), or alternatively, two isoleucines were inserted between alanine and methionine (II-insert). When expressed in human embryonic kidney 293 cells, the D89E mutant was localized intracellularly with no detectable cell surface expression. In contrast, D89N, HR-II, and II-insert mutants displayed cell surface expression, with Kd values and expression levels similar to that of the wild-type transfectant. The ability of the mutants to transduce signal was assessed by ligand-stimulated GTPgamma35S binding, mobilization of intracellular free Ca2+, and chemotaxis assays. Both D89N and HR-II mutants signaled similarly to a wild-type receptor in all three assays. However, the II-insert mutant exhibited a loss of ligand-stimulated GTPgamma35S binding, calcium mobilization, and chemotaxis. Unexpectedly, this receptor underwent ligand-induced sequestration comparable to wild-type CXCR2. These data indicate that Asp89 and the basic amino acids in the third intracellular domain do not play essential roles in ligand-induced signal transduction through CXCR2. However, proper secondary structure and orientation of the third intracellular loop of CXCR2 are essential for ligand-mediated signal transduction but not for receptor sequestration.
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PMID:Interruption of G protein-coupling in CXCR2 does not alter ligand binding, but eliminates ligand-activation of GTPgamma35S binding, calcium mobilization, and chemotaxis. 939 46

We examined secretion, mRNA expression, and histologic localization of interleukin-8 (IL-*) and growth-related gene product-alpha (GRO alpha) in the Helicobacter pylori-infected gastric antral mucosa. Antral biopsies were obtained from an area of endoscopically intact mucosa. Significantly higher levels of IL-8 and GRO alpha were secreted in organ cultures from patients with H. pylori infection, and their elevation was prominent in patients with duodenal ulcer. There was a significant association between these alpha-chemokine levels and histologic grades of activity, inflammation, and H. pylori density. In fresh antral biopsies, IL-8 and GRO alpha mRNA expression was detected more frequently in H. pylori-infected patients compared with those without infection. Immunofluorescence microscopy showed localization of IL-8 and GRO alpha proteins in gastric epithelial cells and infiltrating CD68+ macrophages. In the chemotaxis assay, a significant positive correlation was found between neutrophil migration induced by the organ culture supernatants and their contents of IL-8 and GRO alpha. After H. pylori eradication, a significant decrease was observed in IL-8 and GRO alpha levels detected in organ cultures. In conclusion, mucosal alpha-chemokine activity correlates well with histologic severity of H. pylori-associated antral gastritis and can be used to predict the effects of H. pylori eradication therapy.
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PMID:Mucosal chemokine activity in Helicobacter pylori infection. 947 49

Interleukin-8 (IL-8) acts on human neutrophils via two receptors, CXCR1 and CXCR2. It shares CXCR2 with all neutrophil-activating chemokines, which like IL-8 have a conserved Glu-Leu-Arg (ELR) N-terminal motif, but is generally considered to be the only relevant agonist for CXCR1. IL-8 has a basic residue at the sixth position after the second cysteine, which was suggested to contribute to CXCR1 specificity. Among the other ELR chemokines, only granulocyte chemotactic protein 2 (GCP-2) has such a basic determinant. Using Jurkat cells that stably express either CXCR1 or CXCR2, we studied receptor activation by IL-8, GCP-2 epithelial neutrophil-activating protein 2 (ENA-78) (which shares 77% identical amino acids with GCP-2) and growth-regulated oncogene alpha (GRO alpha). At 10 nM and higher concentrations, GCP-2 and IL-8 induced significant activation of CXCR1-expressing cells, but no activity was found with GRO alpha and ENA-78. As expected, however, all four chemokines had similar activities on CXCR2-expressing cells. A variant of GCP-2 in which the basic residue, Arg20, was replaced by a glycine was synthesized. This derivative was ineffective on CXCR1, but was as active as wild-type GCP-2 in CXCR2-expressing cells. GCP-2 displaced radiolabeled IL-8 from both receptors with low affinity, and in this respect resembled ENA-78 and GRO alpha. Our data show that GCP-2 acts via both IL-8 receptors and thus appears to be functionally more similar to IL-8 than to the other ELR chemokines. Activation of CXCR1 appears to depend significantly on the presence of a basic binding determinant close to the second cysteine.
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PMID:Granulocyte chemotactic protein 2 acts via both IL-8 receptors, CXCR1 and CXCR2. 948 96

The aim of the present study was to determine the efficacy of a new combination regimen including an antioxidant, a proton pump inhibitor, and antibiotics against Helicobacter pylori and to document the changes of oxidative stress and cytokines involved in H. pylori-associated gastric inflammation. From 57 patients with endoscopically diagnosed gastric and/or duodenal ulcers associated with H. pylori infection five gastric antral biopsy specimens were taken for the diagnosis of H. pylori and for the experimental measures. The patients were then treated either with lansoprazole 30 mg + amoxicillin 1.5 g (LA group; 21 patients) or lansoprazole 30 mg + amoxicillin 1.5 g + rebamipide 300 mg (LAM group; 36 patients) for two weeks. Four weeks after the initiation of treatment, the patients were endoscoped again and biopsy specimens were obtained. Mucosal malondialdehyde (MDA) levels; myeloperoxidase (MPO) activities; superoxide dismutase; catalase; glutathione peroxidase; cytokines IL-1, IL-6, TNF-alpha; and chemokines IL-8, GRO-alpha, RANTES (regulated on activation normal T expressed and secreted) were measured. Using paraffin-embedded tissue sections, in situ terminal deoxyribonucleotide transferase (TdT) mediated dUTP nick end labeling (TUNEL) for apoptosis and immunohistochemical staining for inducible nitric oxide synthase (iNOS) were performed. Two weeks of treatment with the LA regimen resulted in 57.4% eradication rates of H. pylori, whereas two weeks of treatment with the LAM regimen resulted in 75.0% eradication rates. Eradication rates between these two groups were statistically significantly different (P < 0.05). Mucosal MDA levels and MPO activities were significantly lower in the LAM group than the LA group. Mucosal levels of cytokines IL-1, IL-6, and TNF-alpha and of chemokines IL-8, GRO-alpha, and RANTES were all significantly decreased after the treatment of H. pylori, especially so in the LAM group. The apoptotic index and iNOS score were significantly reduced after the eradication of H. pylori. The addition of an antioxidative drug to the eradication regimen against H. pylori has advantages either in augmenting the eradication rates of H. pylori or in decreasing the oxidative stress and cytokines levels generated by H. pylori infection.
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PMID:Augmented eradication rates of Helicobacter pylori by new combination therapy with lansoprazole, amoxicillin, and rebamipide. 951 12

We recently described a novel population of blood-borne cells, termed fibrocytes, that display a distinct cell surface phenotype (collagen+/CD13+/CD34+/CD45+), rapidly enter sites of tissue injury, and contribute to scar formation. To further characterize the role of these cells in vivo, we examined the expression of type I collagen and cytokine mRNAs by cells isolated from wound chambers implanted into mice. Five days after chamber implantation, CD34+ fibrocytes but not CD14+ monocytes or CD90+ T cells expressed mRNA for type I collagen. Fibrocytes purified from wound chambers also were found to express mRNA for IL-1beta, IL-10, TNF-alpha, JE/MCP, MIP-1alpha, MIP-1beta, MIP-2, PDGF-A, TGF-beta1, and M-CSF. The addition of IL-1beta (1-100 ng/ml), a critical mediator in wound healing, to fibrocytes isolated from human peripheral blood induced the secretion of chemokines (MIP-1alpha, MIP-1beta, MCP-1, IL-8, and GRO alpha), hemopoietic growth factors (IL-6, IL-10, and macrophage-CSF), and the fibrogenic cytokine TNF-alpha. By contrast, IL-1beta decreased the constitutive secretion of type I collagen as measured by ELISA. Additional evidence for a role for fibrocytes in collagen production in vivo was obtained in studies of livers obtained from Schistosoma japonicum-infected mice. Mouse fibrocytes localized to areas of granuloma formation and connective matrix deposition. We conclude that fibrocytes are an important source of cytokines and type I collagen during both the inflammatory and the repair phase of the wound healing response. Furthermore, IL-1beta may act on fibrocytes to effect a phenotypic transition between a repair/remodeling and a proinflammatory mode.
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PMID:Regulated production of type I collagen and inflammatory cytokines by peripheral blood fibrocytes. 955 99

H. pylori infection leads to gastric inflammation, characterised histologically by surface epithelial degeneration and infiltration of the gastric mucosa by acute and chronic inflammatory cells. H. pylori adherence, the production of a vacuolating cytotoxin and bacterial enzymes all contribute to epithelial damage. Recruitment and activation of immune cells in the underlying mucosa involves H. pylori chemotaxins, epithelial-derived chemotactic peptides (chemokines) such as IL-8 and GRO-alpha, and pro-inflammatory cytokines liberated by mononuclear phagocytes (TNF alpha, IL-1 and IL-6) as part of non-specific immunity. Antigen-specific cellular immunity results in a predominant Th1 lymphocyte response with an increase in IFN-gamma secreting T-helper cells, whilst humoral responses lead to the production of anti-H. pylori antibodies and complement activation. The complex network of cytokines implicated in these inflammatory responses include counter-regulatory elements such as IL-10 which may serve to damp down inflammation. Molecular mimicry of host structures by H. pylori, with the generation of specific immunity directed against self-antigens may also contribute to host injury. Progress in molecular biology has revealed considerable genomic diversity amongst H. pylori strains, with cag+ bacteria being associated with increased chemokine and cytokine responses and more severe degrees of gastric inflammation. Strain hetereogeneity may contribute towards the wide spectrum of disease manifestations encountered in clinical practice.
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PMID:Helicobacter pylori and gastric inflammation. 960 38

The production of monocyte chemoattractant protein-1 (MCP-1) and its regulation by TNFalpha, IL-1, and IL-8 were investigated in two rabbit models of arthritis induced by intra-articular injection of lipopolysaccharide (LPS) or monosodium urate (MSU) crystals. We first prepared recombinant rabbit MCP-1 and antibodies and then developed an immunoassay. The immunoassay detected 3 pg/ml rabbit MCP-1 and did not cross-react with other rabbit chemokines such as IL-8 or GRO. MCP-1 was first detected in synovial fluid (SF) at 1 hour, and peaked at 4 or 2 hours after the injection of LPS or MSU crystals, respectively. Immunohistochemically, MCP-1 was detected in synovial lining cells and infiltrating neutrophils. The amounts of MCP-1 detected in SF from neutrophil-depleted rabbits were similar to those in normal rabbits, suggesting that synovial lining cells were the main source of MCP-1 detected in SF. The peak level of MCP-1 in SF after LPS-injection was inhibited by 57% with anti-TNFalpha mAb and by 41% with IL-1 receptor antagonist (IL-1Ra). Coadministration of anti-TNFalpha mAb and IL-1Ra inhibited 90% of MCP-1 production. In contrast, the peak level of MCP-1 in SF after MSU crystal-injection was not affected by any cytokine inhibitor, but was reduced by 52% with coadministration of anti-TNFalpha mAb and IL-1Ra. Anti-IL-8 IgG had no effect on the production of MCP-1 in either model. Thus, the production of MCP-1 in LPS-induced arthritis was mostly regulated by TNFalpha and IL-1, whereas half the extent of MCP-1 production in MSU crystal-induced arthritis was independent of TNFalpha or IL-1. IL-8 does not seem to regulate the production of MCP-1 in SF either directly or indirectly. Finally, administration of neutralizing anti-MCP-1 antibody inhibited LPS- and MSU crystal-induced monocyte infiltration by 58.4% and 44.9%, respectively, suggesting that synovial production of MCP-1 plays an important role in the recruitment of monocytes in these arthritis models.
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PMID:Production and regulation of monocyte chemoattractant protein-1 in lipopolysaccharide- or monosodium urate crystal-induced arthritis in rabbits: roles of tumor necrosis factor alpha, interleukin-1, and interleukin-8. 971 85


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