Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:P10145 (IL-8)
23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Macrophages are supposed to play a key role in inflammatory and tumor angiogenesis. Their importance derives from (1) their ubiquitous presence in normal and especially inflamed tissues, (2) their potential to become activated in response to appropriate stimuli, and (3) their repertoire of secretory products. By release of proteases, growth factors (bFGF, GM-CSF, TGF-alpha, IGF-I, PDGF, VEGF/VPF, TGF-beta), and other monokines (IL-1, IL-6, IL-8, TNF-alpha, substance P, prostaglandins, interferons, thrombospondin 1), activated macrophages have the capability to influence each phase of the angiogenic process, such as alterations of the local extracellular matrix, induction of endothelial cells to migrate or proliferate, and inhibition of vascular growth with formation of differentiated capillaries. This review describes macrophage physiology and the influence of macrophage secretory products on the different phases of angiogenesis in vitro and in vivo.
...
PMID:Macrophages and angiogenesis. 750 44

The effect of cytokines, growth factors, mitogens, and bacterial products on nitric oxide (NO) generation by monolayers of small intestinal epithelial cells-6 (IEC-6) cells was evaluated. Subconfluent IEC-6 cells were maintained in DMEM containing 5% fetal calf serum and after 16-24 hr of incubation, the medium was replaced with fresh medium in the presence or absence of calcium ionophore (CaI), L-NAME, L-NNA, individual growth factors, cytokines, or mitogens. After 72 hr of culture, the media supernatant was collected and NO chi generation was determined. NO synthase activity was determined in sonicated supernatants of IEC-6 cells by [14C] arginine conversion to citrulline. NO chi generation in subconfluent cultures was greater than in fully confluent cultures, suggesting contact inhibition. NO chi generation by IEC-6 cells was significantly increased by CaI and inhibited by L-NAME and L-NNA. LPS, IL-1 beta, IL-2, IL-8, IFN-8, TFN-alpha, EGF, TGF-alpha, bFGF, and PHA significantly increased NO chi generation. NO synthase activity in IEC-6 cells (4.2 +/- 1.7 pmol/min/10(6) cells) was NADPH dependent. These results suggest that stimulation of NO chi generation by intestinal epithelial cells through cytokine bacterial products and mitogens may be one of the mechanisms responsible for their effects in the intestinal tract.
...
PMID:NO chi generation by cultured small intestinal epithelial cells. 755 34

Signals transmitted from mesenchyme to epithelia or vice versa constitute the basis of reciprocal epithelial-mesenchymal interactions. As a first step toward understanding epithelial-mesenchymal interactions on the ocular surface where the transit amplifying cell-containing corneal epithelium is anatomically separated from the stem cell-containing limbal epithelium, we sought to characterize the expression patterns of cytokines and their receptors by primary epithelial and early-passaged fibroblast cultures of human cornea and limbus. Northern hybridization with oligonucleotide and cDNA probes to a total of 25 cytokines and 12 of their receptors revealed that the positively expressed cytokines could be divided into the following four patterns. Type I: TGF-alpha, IL-1 beta, and PDGF-B were expressed exclusively by epithelial cells but their respective receptors EGFR and IL-1R were predominantly and PDGFR-beta was exclusively expressed by fibroblasts. Type II: IGF-I, TGF-beta 1, -beta 2, LIF, and bFGF, and their receptors were expressed by both epithelial cells and fibroblasts. FGFR-1 (flg) and FGFR-2 (bek) were expressed more by fibroblasts and bFGF was expressed more by corneal than limbal epithelial cells. Type III: keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) were expressed exclusively by fibroblasts and their respective receptors, KGFR and c-met, were predominantly expressed by epithelial cells. Combined with RT-PCR, the quantity of KGF and KGFR transcripts was highest in limbal fibroblasts and epithelial cells, respectively. In contrast, the quantity of HGF and HGFR (c-met) transcripts was highest in corneal fibroblasts and epithelial cells, respectively. Type IV: M-CSF and IL-8 were expressed by fibroblasts and/or epithelial cells but their receptors were not expressed by epithelial cells nor fibroblasts, but by immune or inflammatory cells. In addition to these potential paracrine actions, autocrine actions mediated by TGF-alpha/EGFR, IL-1 beta/IL1-R, and bFGF/FGFR-1 were more expressed by corneal than limbal epithelial cells. Immunofluorescence staining on human corneoscleral cryosections confirmed that EGFR and bFGF were not expressed by the limbal basal epithelium, but expressed strongly by the corneal epithelium, a pattern consistent with Northern hybridization. These results indicate that ocular surface epithelial cells and fibroblasts can express a myriad of cytokines, among which the first three patterns constitute the network of potential epithelial-mesenchymal cytokine dialogues. The difference of certain cytokine expression between corneal and limbal regions suggests that this network participates in normal epithelial growth and differentiation, and plays an important role in wound healing.
...
PMID:Three patterns of cytokine expression potentially involved in epithelial-fibroblast interactions of human ocular surface. 789 1

Transforming growth factor (TGF)-alpha is a pleiotropic polypeptide which mediates a variety of tissue-specific cellular responses such as induction of proliferation, cell migration, vascularization, and formation of extracellular matrix. TGF-alpha is produced by certain tumor cells and embryogenic tissues, as well as by normal cells of different origin. Within the granulocytic lineage, TGF-alpha production has been shown in promyelocytic leukemia cells induced to differentiate, as well as in blood eosinophils of patients with the idiopathic hypereosinophilic syndrome. The present study was carried out in order to examine expression of the TGF-alpha gene in polymorphonuclear (PMN) and mononuclear (MN) blood cells of normal healthy donors. While MN and neutrophilic PMN failed to synthesize TGF-alpha transcripts and protein, eosinophils constitutively exhibited TGF-alpha transcripts accompanied by the release of immunoreactive TGF-alpha protein. Exposure of PMN and MN cells to the leukocyte-activating cytokines interleukin (IL)-3, IL-5, and granulocyte-macrophage colony-stimulating factor resulted in a several-fold increase of TGF-alpha mRNA expression and protein release by eosinophils, but not by neutrophils and MN cells. PMN and MN were insensitive to induction of TGF-alpha release by IL-8 and granulocyte colony-stimulating factor. These results point to a functional role of eosinophils in disorders characterized by unbalanced TGF-alpha production such as disease states associated with abnormal matrix formation and neovascularization which may be explained by the present demonstration of TGF-alpha production in these cells.
...
PMID:Expression of the transforming growth factor-alpha gene by human eosinophils is regulated by interleukin-3, interleukin-5, and granulocyte-macrophage colony-stimulating factor. 812 34

The purpose of this study was to investigate and to compare, by in situ hybridization, gene expression of IL-1 beta, IL-8, TGF-beta 1, TGF-beta 2, TGF-beta 3, TGF-alpha, p53 and c-myc in lesions and in non-involved skin of patients with psoriasis. All lesional skin biopsies showed overexpression of IL-1 beta, IL-8 TGF-alpha mRNAs. IL-1 beta hybridization signals were strong in a small number of cells localized predominantly in the dermal papillae and in the suprapapillary epidermis. Overexpression of TGF-alpha was observed in all suprabasal keratinocytes, whereas strongly elevated IL-8 mRNA expression was found to be restricted to clusters of suprabasal keratinocytes. TGF-beta 3, p53 and c-myc transcripts were clearly detected in the epidermis of all biopsies, although expression levels were comparable in lesional and non-lesional skin.
...
PMID:In situ hybridization analysis of cytokine, proto-oncogene and tumour suppressor gene expression in psoriasis. 821 83

This review concentrates on growth autonomy of tumor cells in relation to tumor progression. Human malignant melanoma serves as an example for progressive growth factor independence at subsequent stages of tumor progression. Mechanisms by which malignant cells acquire growth factor independence are discussed. In melanoma, deregulation of growth regulatory pathways has been described on four levels: 1) aberrant production of autocrine growth factors that substitute for exogenous growth factors (basic fibroblast growth factor [bFGF]); 2) alterations in the response to negative autocrine growth factors (interleukin [IL]-6 and transforming growth factor [TGF]-beta); 3) overexpression of epidermal growth factor receptors (EGF-R); and 4) alterations of cellular protooncogenes involved in signal transduction (RAS, MYB) and growth suppression (p53). In addition to bFGF and IL-6, multiple other growth factor genes are activated in malignant melanoma cells but not normal melanocytes. These include both chains of platelet-derived growth factor (PDGF), TGF-alpha, IL-1, IL-8, and tumor necrosis factor (TNF)-alpha. Of these, PDGF-B has been investigated in more detail. Melanoma-derived PDGF clearly does not act in a direct autocrine mode, but has important paracrine effects on normal tissue constituents, notably fibroblasts and endothelial cells, that are essential for tumor development in vivo. It is speculated that other melanoma-derived growth factors with as yet undefined functions similarly exert such paracrine or 'indirect' autocrine effects that cannot be sufficiently addressed in studies on cultured cells.
...
PMID:Growth factor independence and growth regulatory pathways in human melanoma development. 828 9

Normal melanocytes require a number of exogenous growth factors in contrast to most metastatic malignant melanomas. This investigation demonstrates that endogenously produced human IL-8 can act as an important growth factor for human melanoma cells. In the present study, six out of eight human melanoma cell lines tested secrete IL-8 protein into the culture supernatant. In two of these IL-8-secreting melanoma cell lines, SK-MEL 13 and SK-MEL 23, we have determined the IL-8 requirement for their proliferative capacity. These melanoma cell lines produced significant amounts of bioactive IL-8 as measured by the ELISA technique. Secretion of human IL-8 was inducible by IL-1 and by PMA. Human IL-8-specific mRNA was already detected in unstimulated melanoma cells. In addition, human IL-8-R mRNA could be detected for the first time in human melanoma cells. Exposure of the two melanoma cell lines in vitro to antisense oligonucleotides targeted against two different sites of human IL-8 mRNA-inhibited cell proliferation, colony formation in soft agar, and secretion of IL-8 protein into culture supernatant in a dose dependent fashion. Effects were reversible either by removal of the oligomers or by addition of exogenous IL-8 protein. In contrast, exposure to IL-8 sense probes or oligonucleotides in sense or antisense orientation specific for IL-7, TGF-alpha, TGF-beta, and MGSA had no such effect. A monospecific immune serum and two IL-8-specific mAb were also capable of inhibiting melanoma cell proliferation in the same manner. These results provide strong evidence for an autocrine IL-8 synthesis and for an IL-8-dependent proliferation in a subgroup of human melanomas. Furthermore, they suggest that IL-8 may play a role not only in immunomodulation but also in melanoma progression and metastatic spread.
...
PMID:IL-8 produced by human malignant melanoma cells in vitro is an essential autocrine growth factor. 808 4

We investigated the regulation of elastase activity in murine peritoneal macrophages by different cytokines and bacterial LPS. Thioglycolate-elicited mouse peritoneal exudate macrophages secrete a metalloproteinase that degrades elastin. Incubation of peritoneal exudate macrophages with LPS and IFN-gamma significantly inhibited the production of elastase by a mechanism independent of nitric oxide, superoxide, and hydrogen peroxide. The cytokines IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, TNF, TGF-alpha and -beta, basic fibroblast growth factor, monocyte chemotactic factor-1, and granulocyte CSF (G-CSF) had no significant effect on the production of elastase by macrophages. In contrast, granulocyte-macrophage CSF (GM-CSF) increased the production of elastase in a dose-dependent manner, and with macrophage CSF (M-CSF) inhibited it. Elastin zymography demonstrated that the modulation of elastolytic activity in macrophages was associated with changes in the level of metalloelastase protein. The stimulation of elastase activity by GM-CSF and the inhibition of elastase activity by LPS, IFN-gamma, and M-CSF occurred at the level of transcription. LPS and M-CSF also augmented the expression level of tissue inhibitors of metalloproteinase mRNA. The increased mRNA steady state level of murine macrophage elastase induced by GM-CSF resulted from both increased transcription and enhanced stability. The modulation of metalloelastase activity in macrophages by IFN-gamma, M-CSF, and GM-CSF suggests that these molecules may control the degradation of elastin fibers in lungs or blood vessels.
...
PMID:Differential regulation of metalloelastase activity in murine peritoneal macrophages by granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor. 894 20

Biologic dressings are believed to stimulate wound healing in a variety of wound types. Cryopreserved allograft skin (CAS) is used as a biologic dressing for excised wounds, partial-thickness wounds, and meshed split-thickness skin grafts, and the use of allogenic or autologous cultured epithelial sheets (CES) has been reported to enhance healing of skin ulcers and deep partial-thickness wounds. However, limitations of allograft skin include bacteriologic and viral safety, limited availability, cost, and ease of handling. Previously we have reported the successful use of human keratinocytes cultured to single-layer confluence on Hydroderm polyurethane membranes (HD/HK) for grafting of full-thickness wounds. In this study we evaluated the release of five different growth peptides (transforming growth factors alpha and beta (TGF-alpha, TGF-beta), interleukin-6, interleukin-8, and melanoma growth stimulatory activity from CAS, CES, and HD/HK grafts. Highest levels of TGF-alpha were found for HD/HK (728 +/- 115 pg/10 cm2 of membrane) followed by CES (491 +/- 137 pg/10 cm2; NS). No TGF-alpha was detectable for CAS, and 3.7-fold, and 25-fold higher levels of interleukin-6 were found for CES (257 +/- 12.7 U/10 cm2) compared with HD/HK and CAS, respectively. Interleukin-8 had similar levels for CES (0.65 +/- 0.7 ng/10 cm2) and HD/HK (0.88 +/- 0.12 ng/10 cm2), whereas melanoma growth stimulatory activity was elevated in CES (2314 +/- 97 pg/10 cm2) compared with HD/HK (1071 +/- 55 pg/10 cm2). TGF-beta was barely detectable for CES and HD/HK. Cryopreserved allograft showed high levels of TGF-beta (5.2 +/- 1.6 ng/10 cm2). Overall mitogenic activity of the supernatants on keratinocyte cultures was assessed. Highest proliferation was seen for CES supernatants followed by HD/HK (NS). Supernatants from CAS had an antiproliferative effect on keratinocytes. We conclude that a single layer of keratinocytes cultured on a polyurethane membrane facilitates keratinocyte proliferation similar to CES, whereas cryopreserved allograft has no mitogenic effect on keratinocytes.
...
PMID:Growth peptide release from biologic dressings: a comparison. 895 39

Evidence suggests an association between alcohol consumption and psoriasis. This relationship is still undefined, although long-term alcohol intake influences the immune system. Interactions between T cells and keratinocytes are important for the pathogenesis of psoriasis, by secretion of pro-inflammatory cytokines and growth factors in psoriatic skin. IL-2, IL-6, IL-8, IFN-gamma and TGF-alpha are hallmark cytokines in a psoriatic cytokine network. We investigated whether ethanol influences the secretion of these cytokines using a co-culture model with keratinocytes from psoriatic patients (n = 9) or from healthy controls (n = 9), with HUT 78 lymphocytes, and determined the cytokine levels with or without ethanol treatment in the culture supernatants. TGF-alpha and IFN-gamma levels were elevated in the ethanol-treated psoriatic co-cultures, to 150% and 175% respectively, but neither in co-cultures with keratinocytes derived from healthy control individuals nor in monocultures. Treatment with ethanol elevated slightly the IL-6 levels in the monocultures from psoriatic and control keratinocytes to 125% but not in HUT 78 monocultures. In the psoriatic co-cultures, IL-6 levels were elevated in the culture supernatants to almost 160%, but they were not influenced by ethanol in co-cultures with control keratinocytes. The cytokine levels of IL-8 or IL-2 were not significantly influenced in the psoriatic mono- and co-cultures or in HUT 78 cultures. If ethanol influences the cytokine secretion of psoriatic keratinocytes and HUT 78 lymphocytes in co-culture conditions, these data suggest that ethanol could also influence the psoriatic cytokine network in vivo, which may explain the explain the aggravation of this disease in alcohol-consuming psoriatic patients.
...
PMID:Ethanol enhances the IFN-gamma, TGF-alpha and IL-6 secretion in psoriatic co-cultures. 897 75


1 2 3 4 Next >>

---