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)

Changes in cytosolic free Ca2+ influence important granulocyte functions like chemotactic behavior, adherence to endothelia, and phagocytosis. In the following study we used a simple reproducible procedure involving flow cytometry in combination with the fluorescent dye Fluo-3 to measure Ca2+ changes in human granulocytes. The aim of our study was to investigate the involvement of protein kinase C in regulating cytosolic free Ca2+ concentrations after stimulation of cells with IL-8 and fMLP. Both reagents induced a 5-6 fold increase in cytosolic Ca2+. Experiments conducted in Ca(2+)-free media showed a minor 18-29% decrease in cytosolic Ca2+ response, suggesting that intracellular Ca(2+)-stores are the main source for Ca2+ release after fMLP or IL-8 stimulation. Activators of protein kinase C, phorbol myristate acetate (PMA) and 1-oleyl-2-acetyl-sn-glycerol (OAG), inhibited cytosolic Ca(2+)-increase completely when induced by IL-8 and by 68-82% in the case of fMLP. Staurosporine, an inhibitor of protein kinase C, was able to attenuate or even abolish the PMA/OAG-effect. Our results show that changes in cytosolic Ca2+ due to IL-8 and fMLP signalling can be regulated by protein kinase C in human granulocytes. This regulatory role of protein kinase C involves some form of receptor modulation (i.e. phosphorylation, internalization, shedding).
Biochem Biophys Res Commun 1993 Dec 15
PMID:Protein kinase C regulates IL-8 and fMLP induced cytoplasmic Ca2+ increase in human granulocytes by receptor modulation measurements by flow cytometry. 826 89

Chronic pulmonary infection with Pseudomonas aeruginosa continues to be the major cause of morbidity and mortality in cystic fibrosis (CF). Several characteristics of CF, including the excessive influx of neutrophils into the airways, cachexia, and hyperglobulinemia, could reflect the effects of cytokines, such as interleukin-1 (IL-1), IL-6, IL-8, and tumor necrosis factor (TNF-alpha). We hypothesized that these pro-inflammatory cytokines, produced by alveolar macrophages in response to pseudomonas and/or other microorganisms, promote the destructive inflammatory process in the lung. We evaluated bronchoalveolar lavage (BAL) fluid and BAL macrophages from 22 CF patients and 13 healthy control (HC) subjects, measuring soluble TNF-alpha, IL-1 beta, IL-6, and IL-8 and the regulatory molecules TNF soluble receptor (TNF-sR), IL-1 receptor antagonist (IL-1Ra), and IL-10 (cytokine synthesis inhibitory factor). Levels of the proinflammatory cytokines were higher in CF versus HC BAL (p < or = 0.05 for IL-1, TNF, and IL-8; p = 0.06 for IL-6). In contrast, HC BAL contained significantly more IL-10 than CF BAL (p < 0.05), but TNF-sR and IL-1Ra were similar. Immunocytochemistry demonstrated a higher percentage of CF than control BAL macrophages expressing intracellular cytokines (p < 0.05). Thus, enhanced macrophage production of proinflammatory cytokines and decreased production of the regulatory molecule IL-10 may have important roles in the pathogenesis of CF lung disease.
Am J Respir Crit Care Med 1995 Dec
PMID:Inflammatory cytokines in cystic fibrosis lungs. 852 Jul 83

Cytokine networks between immune and nonimmune cells of the alveolar-capillary membrane are necessary for cellular communication during pulmonary inflammation. The subsequent events of these cellular/humoral interactions are pivotal to the initiation and propagation of the inflammatory response leading to pulmonary injury. The studies cited in this paper underscore the interrelationship of early response cytokines, adhesion molecules, and the chemokine IL-8 that orchestrate the recruitment of neutrophils into the lung. The paradigm for neutrophil extravasation is likely operative in the microvasculature of the lung, and consists of four or more steps (Figure 3). First, acute lung injury results in the activation of microvascular endothelium in response to the local generation of TNF or IL-1, leading to expression of endothelial cell-derived E- and P-selectins and ICAM-1. The constitutive presence of neutrophil-derived L-selectin allows for the initial adhesive interaction of neutrophils with endothelial cell selectins leading to the "rolling" effect. Second, generation of IL-8 leads to the activation of neutrophils in the vascular compartment and expression of beta 2 integrins, while L-selectin is concomitantly shed. Third, the interaction of the neutrophil beta 2 integrin with its receptor/ligand, ICAM-1, results in the rapid arrest of neutrophils on the endothelium. Fourth, the subsequent events leading to neutrophil extravasation beyond the vascular compartment are dependent upon a combination of haplotaxis (migration in response to an insoluble gradient), the continued expression of beta 2 integrins on neutrophils and ICAM-1 on nonimmune cells, and the maintenance of a neutrophil specific (IL-8) chemotactic gradient. The participation of IL-8 and potentially other C-X-C chemokines in the inflammatory response appears to be critical for the orchestration of the directed migration of inflammatory leukocytes into the lung. After arriving in the lung, these activated leukocytes can respond to noxious stimuli or induce pulmonary injury through the release of reactive oxygen metabolites, proteolytic enzymes, and additional cytokines. Our current knowledge and future investigations regarding the mechanisms involved in neutrophil elicitation may allow us to employ clinical interventional strategies that will attenuate neutrophil-dependent acute lung injury, such as ARDS.
J Investig Med 1994 Dec
PMID:Acute lung injury: the role of cytokines in the elicitation of neutrophils. 852 Oct 27

During intestinal disease induced by Salmonella typhimurium transepithelial migration of neutrophils (PMN) rapidly follows attachment of the bacteria to the epithelial apical membrane. Among the events stimulated by these interactions is the release of chemotaxins that guide PMN through the subepithelial matrix and subsequently through the epithelium itself (McCormick, B.A., S.P. Colgan, C. Delp-Archer, S.I. Miller, and J.L. Madara. 1993. J. Cell Biol. 123:895-907). Given the substantial volume flow that normally characterizes matrix compartments underlying transporting epithelia, it is unclear how such transmatrix signaling is sustained. Here we show that when underlying matrices are isolated from biophysically confluent polarized monolayers of the human intestinal epithelial cell line T84, they fail to support substantial transmatrix migration of PMN unless an exogenous chemotactic gradient is imposed. In contrast, such matrices isolated from confluent monolayers apically colonized with S. typhimurium support spontaneous transmatrix migration of PMN. Such chemotactic imprinting of underlying matrices is resistant to volume wash and is paralleled by secretion of the known matrix-binding chemokine IL-8. Chemotactic imprinting of the matrix underlying S. typhimurium-colonized monolayers is dependent on epithelial protein synthesis, is directional implying the existence of a gradient, and is neutralized by antibodies either to IL-8 or to the IL-8 receptor on PMN. An avirulent S. typhimurium strain, PhoPc, which attaches to epithelial cells as efficiently as wild-type S. typhimurium, fails to induce basolateral secretion of IL-8 and likewise fails to imprint matrices. Together, these observations show that the epithelial surface can respond to the presence of a luminal pathogen and subsequently imprint the subepithelial matrix with retained IL-8 gradients sufficient to resist washout effects of the volume flow that normally traverses this compartment. Such data further support the notion that the primary role for basolateral secretion of IL-8 by the intestinal and likely other epithelia is recruitment of PMN through the matrix to the subepithelial space, rather than directing the final movement of PMN across the epithelium.
J Cell Biol 1995 Dec
PMID:Surface attachment of Salmonella typhimurium to intestinal epithelia imprints the subepithelial matrix with gradients chemotactic for neutrophils. 852 15

Chronic GnRH agonist therapy lowers androgens and decreases androgen-dependent hair shaft diameter, but the resulting induction of hypoestrogenemia has limited its usefulness as a single agent. Estrogen- and progestin-containing oral contraceptives also reduce circulating androgen levels and are commonly used empirically for the treatment of hirsutism, but have not been evaluated in a blinded randomized controlled fashion. The present study is the first double masked trial to evaluate the combination use of a GnRH agonist and an estrogen-containing oral contraceptive and tests our hypothesis that these could synergistically reduce androgen levels and suppress hormone-dependent hair growth while avoiding the symptoms and risks of agonist-induced hypoestrogenemia. We enrolled 64 women in a 24-week blinded randomized controlled trial to compare placebo, nafarelin (NAF; 400 micrograms, intranasal spray, twice daily), norethindrone (1 mg), and ethinyl estradiol (NOR 1/35; 0.035 mg, daily, for 3 of 4 weeks), or combined use of NAF and NOR 1/35 for 24 weeks. At baseline and every 8 weeks, we measured gonadotropins, estrogens, androgens, and hair growth. Bone density was assessed by dual energy x-ray adsorptiometry, and hot flashes were measured objectively. Baseline total testosterone (T), free T, percent free T, and sex hormone-binding globulin-binding capacity were similar among groups. With treatment, significant reductions (P = 0.01) in total T were seen with combination and NAF only therapy. Significant increases (P < 0.001) in the sex hormone-binding globulin-binding capacity were seen in women given NOR 1/35 alone or in combination with NAF. Free T levels decreased to approximately half of baseline levels with combination treatment (17.9 to 6.4 nmol/L; P < 0.001) and NOR 1/35 alone (20.8 to 10.2 nmol/L; P < 0.001). There was a significant decrease in hair shaft diameter after combination therapy (P < 0.05) that was not seen with either agent alone. Combination therapy also prevented the hot flashes and bone loss that occurred with agonist alone. In summary, our results demonstrate that combination GnRH agonist and low dose oral contraceptive therapy is more effective than either agent alone in the treatment of hirsutism and avoids the hypoestrogenic complications that occur with agonist only therapy.
J Clin Endocrinol Metab 1995 Dec
PMID:Comparison of a gonadotropin-releasing hormone agonist and a low dose oral contraceptive given alone or together in the treatment of hirsutism. 853 May 74

NAP-1, a protein first isolated from mammalian cells, can introduce supercoils into relaxed circular DNA in the presence of purified core histones. Based on its in vitro activity, it has been suggested that NAP-1 may be involved in nucleosome assembly in vivo. We isolated a cDNA clone encoding a soybean NAP-1 homolog, SNAP-1. The SNAP-1 cDNA contains an open reading frame of 358 amino acids residues with a calculated molecular weight of 41 kDa. The deduced amino acid sequence of SNAP-1 shares sequence similarity with yeast NAP-1 (38%) and human hNRP (32%). Notable features of the deduced sequence are two extended acidic regions thought to be involved in histone binding. SNAP-1 expressed in Escherichia coli induces supercoiling in relaxed circular DNA, suggesting that SNAP-1 may have nucleosome assembly activity. The specific activity of SNAP-1 is comparable to that of HeLa NAP-1 in an in vitro assay. Western analysis reveals that SNAP-1 is expressed in the immature and young tissues that were examined, while mature tissues such as old leaves and roots, show very little or no expression. NAP-1 homologs also appear to be present in other plant species.
Mol Gen Genet 1995 Dec 15
PMID:Molecular cloning and functional characterization of a cDNA encoding nucleosome assembly protein 1 (NAP-1) from soybean. 854 12

To determine the immune processes involved in chronic liver allograft rejection (CR) we examined in situ cytokine production in tissue from 15 patients with both clinical and histopathological diagnoses of CR. Total RNA was isolated from liver samples, reverse-transcribed and analyzed by RT-PCR for the production of proinflammatory cytokines and immunoregulatory mediators. Transcripts for the Th1-like cytokines IL-2 and IFN-gamma were detected in 53.3% and 46.7% of CR grafts, while they were detected in only 16% and 0% of stable grafts, respectively. The cytotoxic T cell mediator granzyme B was expressed in the majority of liver grafts undergoing CR, but was expressed only in a minority of stable grafts (80% vs. 16%, P < 0.05). The T cell product IL-5 was also significantly upregulated in CR as compared with stable livers (80% vs. 16%, P < 0.01). Other Th2 cytokines--IL-4 and IL-10--and macrophage products--IL-1 beta, IL-6, IL-8, TGF-beta, and TNF-alpha--were not substantially upregulated in CR grafts as compared with stable grafts. PDGF-beta transcripts were detected in the majority of the CR grafts, but were not detected in stable liver grafts (73% vs. 0, P < 0.05). By immunohistochemical staining, we observed that CD3+CD4+, and CD3+CD4- T cells were detected in CR grafts along with CD20+ B cells and CD68+ macrophages. There was, however, a predominant infiltration of CD3+CD4+ lymphocytes. Taken together, these data suggest that infiltrating cells produce proinflammatory and immunoregulatory cytokines that have a role in mediating graft damage in CR.
Transplantation 1995 Dec 27
PMID:Expression of cytokines and immune mediators during chronic liver allograft rejection. 854 86

The scientific interest in the physical interaction of Plasmodium falciparum-infected erythrocytes with host cells stems from the suggestion that excessive binding in the microvasculature leads to severe malaria. The authors studied, therefore, two parasites for their ability to adhere to normal human cells and to induce cytokine production, one parasite lacking a binding capacity (DD2) and one which adhered to CD36+ transfected CHO cells (MCAMP). The MCAMP parasites readily bound to platelets and erythrocytes and to monocytes, polymorphonuclear granulocytes and EBV-transformed B cells as seen by light and electron microscopy. Platelets were frequently attached in large numbers to the infected erythrocyte surface and groups of infected erythrocytes were sometimes held together by several platelets. Nine out of 17 cytokines tested were found to be secreted into the culture supernatants after 35 h of co-cultures containing monocytes or unfractionated peripheral blood mononuclear cells (PBMC) and parasites (IL-1RA, IL-6, IL-8, IL-10, TGF beta, TNF alpha, G-CSF, IL-1-beta, and GM-CSF). Three additional cytokines were also present in low levels (< 200 pg/ml, IL-2, IL-4, IFN gamma) in the culture supernatants after incubation of the cells for 4 days. TNF alpha, IL-RA, and IL-8 were secreted from polymorphonuclear granulocytes, LGLs and T cells. Platelets and, to a lesser degree, monocytes and T cells secreted large amounts of TGF beta (10-30 ng/ml). Cytokines may participate in the pathogenesis but also the suppression of immune responses seen during acute malarial infections.
Scand J Immunol 1995 Dec
PMID:Adhesion of Plasmodium falciparum-infected erythrocytes to human cells and secretion of cytokines (IL-1-beta, IL-1RA, IL-6, IL-8, IL-10, TGF beta, TNF alpha, G-CSF, GM-CSF. 855 86

To clarify the mechanism of action of immunoglobulin (IgG) in intravenous immunoglobulin therapy for ulcerative colitis (UC) patients, we studied the effect of IgG on the dynamics of immunocompetent cells in the colonic mucosa of experimental colitis induced by dextran sulfate sodium (DSS) in rats. The administration of the same species' IgG suppressed the mucosal infiltration of immunocompetent cells (activated T cells, macrophages and neutrophils), although the different species' IgG didn't. We have already shown that the same species' IgG, suppressed the production of inflammatory cytokines (TNF alpha, IL-1 alpha and IL-8) in the colonic mucosa of experimental colitis induced by DSS. In the present report, we demonstrated the different species' IgG, as well as same species' IgG, suppressed the production of inflammatory cytokines (TNF alpha and IL-1 alpha) from lamina propria mononuclear cells of rat large intestine in vitro. Therefore, it was considered that the suppression of cytokine production was a consequence of the decreased immunocompetent cells in colitis mucosa. Furthermore, we demonstrated that the DSS-treated antigen presenting cells (APCs) activated antigen-specific T cells as a possible mechanism underlying the colitis induced by DSS and the same species' IgG inhibited this activation of T cells.
Nihon Shokakibyo Gakkai Zasshi 1995 Dec
PMID:[Immunological effect of immunoglobulin on experimental colitis induced by dextran sulfate]. 855 75

We have examined the effects of mercuric chloride (HgCl2) on growth and IL-4, IL-8, TNF-alpha and MHC class II gene expression in the HMC-1 human leukemic mast cell line. Proliferation, measured by [3H]thymidine incorporation or production of a formazan product (MTT assay), was substantially inhibited by HgCl2 at concentrations of 10(-6) M and above. Inspection of the DNA by agarose gel electrophoresis from HgCl2-treated cells revealed that it was intact, indicating inhibition of DNA synthesis, but not denaturation. HgCl2 inhibited expression of mRNA for IL-8, TNF-alpha and MHC class II at 4 x 10(-6) M and inhibited expression of IL-4 mRNA at 8 x 10(-6) M and above. At a concentration of 10(-5)M, HgCl2 almost completely blocked mRNA expression for IL-4, IL-8, TNF-alpha and MHC class II, but produced negligible inhibition of expression of mRNA encoding the housekeeping gene beta-actin, thus demonstrating selective toxicity for the cytokine and MHC class II genes studied. Pre-exposure of the cells to human recombinant IL-4 prior to treatment with HgCl2 had no effect on expression levels of any of the genes examined. The effects seen in this study are consistent with previous reports showing immunotoxic effects of HgCl2 on other cell types, therefore, the HMC-1 mast cell line may prove useful in further studies of mast cell cytokine gene expression and the mechanisms involved in cytokine gene toxicity.
Toxicology 1995 Dec 15
PMID:The effects of mercuric chloride on growth, cytokine and MHC class II gene expression in a human leukemic mast cell line. 856 Apr 97


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