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)

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.
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PMID:Macrophages and angiogenesis. 750 44

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.
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PMID:Three patterns of cytokine expression potentially involved in epithelial-fibroblast interactions of human ocular surface. 789 1

Ezrin is a membrane-cytoskeleton linker protein and belongs to the TERM family. It has been implicated in the membrane ruffling, motility, and metastatic process of tumour cells. This study examined the effects of a range of cytokines on the expression of ezrin in the human colon cancer cell line, HT29. Levels of ezrin were determined by Northern and Western blotting and indirect immunofluorescence. We report that IL-2, IL-8, IL-10 and IGF-I had an inhibitory effect on the expression, whereas EGF and IL-11 enhanced cellular ezrin levels. Immunofluorescence confirmed that these changes were seen both in cytosol and generalised membrane. It is concluded that ezrin expression in tumour cells can be regulated by cytokines and this bears importance in the understanding of its role in tumour biology.
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PMID:Cytokine regulation of ezrin expression in the human colon cancer cell line HT29. 868 42

Tumour development and progression involves the expression of oncogenes and inactivation of tumour suppressor genes, leading to the appearance of multiple malignant characteristics. Malignant melanoma cells express different growth factors and cytokines and their receptors in respective stages of tumour progression, which by autocrine and paracrine effects enable them to grow autonomously and confer competence to metastasis. Autocrine growth factors (bFGF, MGSA/GRO, IL-8 and sometimes IL-6, PDGF-A, IL-10) produced by melanoma cells stimulate proliferation of the producing cell itself, while paracrine growth factors (for example PDGF, EGF, TGF-beta, IL-1, GM-CSF, IGF-I, NGF, VEGF) modulate the microenvironment to the benefit of tumour growth and invasion. Paracrine effects include angiogenesis, stroma formation, modulation of host immune response, activation of proteolytic enzymes, adhesion or motility and metastasis formation. Some growth factors have inhibitory effects on melanocytes and early lesions (IL-1, IL-6, TGF-beta, OSM, TNF and IFN) but not on advanced stage melanomas, and in some cases they switch to autocrine stimulator (IL-6, TGF-beta). Understanding the involvement of different growth factors and cytokines in the molecular mechanism of melanoma progression will help to provide an insight into new future therapeutic approaches for melanoma.
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PMID:Autocrine and paracrine regulation by cytokines and growth factors in melanoma. 1084 28

Levels of messenger RNA (mRNA) extracted from five samples of radicular cyst-lining epithelium were analyzed for cytokines, growth factors and epithelial cell growth-related receptors by RT-PCR. All five samples expressed IL-1alpha, -1beta, IL-6, IL-8, IL-11, TGF-beta1, PDGF-A and aFGF, and receptors for EGF (c-erbB), KGF, HGF (c-met) and IL-6. Some of the specimens expressed MIP-1alpha, RANTES, GM-CSF, M-CSF, TNF-alpha, PDGF-B and bFGF, but no expression of IL-2, IL-4, IFN-gamma, IGF-I, EGF and KGF was detected. These results indicate that radicular cyst-lining epithelium, which is considered to be identical to the cell rests of Malassez, may play a role in periodontal pocket formation or apical cyst formation by interaction with surrounding connective tissue or hematopoietic cells through the expression of various cytokines.
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PMID:Profiles of cytokine expression in radicular cyst-lining epithelium examined by RT-PCR. 1126 83

Granulocytes are key cells in inflammatory processes that are recruited to sites of inflammation by chemoattractants such as IL-8 produced by neutrophils and monocytes. Programmed cell death (apoptosis) of granulocytes and subsequent recognition and phagocytosis by macrophages is a crucial mechanism for resolution of inflammation. Because IGF-I is a potent antiapoptotic factor, we addressed the effects of IGF-I on in vitro apoptosis of human peripheral blood granulocytes. We detected 1390 +/- 467 IGF-I receptors with a dissociation constant of 2.3 +/- 0.9 nM on purified granulocytes. Using microscopical analysis, annexin V binding assays to detect relocation of phosphatidylserine to the cell surface, and DNA fragmentation assays, we showed that IGF-I inhibits spontaneous apoptosis of granulocytes in serum-free culture by 32-45%. IGF-I did not modulate the secretion of IL-6, TNF alpha, and IL-8 by granulocytes, but IL-8 secretion by peripheral blood mononuclear cells was enhanced by 40%. These observations indicate that IGF-I may promote granulocyte functions by increasing granulocyte longevity.
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PMID:Igf-I inhibits spontaneous apoptosis in human granulocytes. 1189 74

Interleukin (IL)-8 serves as a major chemoattractant for neutrophils and has also been proposed to affect cancer progression. In the present study, we show that IGF-I stimulates IL-8 mRNA expression and IL-8 secretion in the leukemic cell line HL-60. Stimulation of IL-8 expression was completely attenuated by two inhibitors of mitogen-activated protein kinase (MAPK) kinase (MEK), which phosphorylates the MAPKs extracellular-regulated kinase (ERK)1 and ERK2, and by the c-Jun NH2-terminal kinase (JNK) inhibitor SP600125. In contrast, inhibitors of p38 MAPK and phosphatidylinositol-3 kinase (PI3K) did not abrogate the effect of IGF-I. We also show that IGF-I stimulates the activation of ERK1 and ERK2, but we could not detect any effect of IGF-I on the phosphorylation of p38, JNK(p46) or JNK(p54). Collectively, our results suggest that basal JNK activity and activation of the MEK-ERK pathway are required for upregulation of IL-8 by IGF-I in HL-60 cells.
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PMID:IGF-I stimulates IL-8 production in the promyelocytic cell line HL-60 through activation of extracellular signal-regulated protein kinase. 1457 64

There is vast body of evidence that the insulin-like growth factor (IGF)-I exerts immunomodulatory effects in vitro and in vivo. In vitro studies indicate that stimulatory effects of IGF-I may be exerted through augmentation of inflammatory cytokine production. To further explore the immunomodulatory effects of IGF-I through regulation of cytokine production, we tested the in vitro effects of IGF-I on the secretion of inflammatory T helper cell type 1 (Th1) and Th2 cytokines by human peripheral blood mononuclear cells (PBMC). To this end, PBMC were stimulated with the T cell mitogen phytohemagglutinin (PHA), and cytokines in the culture media were assessed after 18, 42, 66, and 80 h of culture. We found that IGF-I stimulated the secretion of the Th2 cytokine interleukin (IL)-10 by 40-70% in PHA-stimulated PBMC. In addition, we observed a small stimulatory effect (15%) on the secretion of another Th2 cytokine IL-4. The secretion of IL-2, IL-5, IL-6, interferon-gamma, and the inflammatory cytokines IL-1beta, IL-8, and tumor necrosis factor alpha was not or was hardly affected. IL-10 secretion was also stimulated in purified T cells, and we established that IGF-I also stimulated IL-10 mRNA expression by 100-150%. The monocyte-activating bacterial cell-wall product lipopolysaccharide induced IL-10 production in PBMC, but this was not affected by IGF-I. As IL-10 predominantly exerts anti-inflammatory actions and suppresses Th1-dependent immune responses, our results indicate that IGF-I may exert inhibitory actions on inflammatory and Th1-mediated cellular immune responses through stimulation of IL-10 production in T cells.
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PMID:Insulin-like growth factor-I stimulates IL-10 production in human T cells. 1527 70

We previously established that stimulation by IGF-I of interleukin (IL)-8 expression in leukocytes required activation of extracellular-regulated kinase (ERK) and basal activity of c-Jun N-terminal kinase (JNK). In this study, we tested the hypothesis that IGF-I stimulates IL-8 expression at the transcriptional level through induction of Fos/Jun activator protein (AP)-1 complex formation. Inhibition studies using the transcriptional inhibitor actinomycin D and IL-8 promoter activation studies indicate that IGF-I act at the transcriptional level. Using gel shift assays we demonstrate that IGF-I induces the formation of active c-Jun/c-Fos AP-1 complexes. Promoter activation studies using mutated IL-8 promoter constructs show that the AP-1 response element is required for promoter activation by IGF-I whereas CAAT-enhancer binding protein (C/EBP) and nuclear factor of kappa B (NFkappaB) sites were not essential. These results indicate that IGF-I can augment IL-8 expression through activation of AP-1 independent of other inducible transcription factors which have shown to be involved in IL-8 regulation by immune stimuli. This finding is in agreement with our previous observation that IGF-I is able to enhance basal IL-8 production in peripheral blood mononuclear cells (PBMC) in the absence of other stimuli.
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PMID:Insulin-like growth factor-I augments interleukin-8 promoter activity through induction of activator protein-1 complex formation. 1684 47

Our recent clinical studies have demonstrated that autologous implantation of human cultured periosteal (hCP) sheets in combination with porous hydroxylapatite (HAp) particles at the site of periodontal bone defects strikingly facilitates tissue regeneration. To better understand how the hCP sheet functions at the implantation site, we have now examined its biochemical and morphological characteristics in vitro and its ectopic osteoinductivity in nude mice. Cultured human periosteal tissue segments produced periosteal cells that migrated out from the central region within 4-8 days and grew more rapidly with longer culture times. Alkaline phosphatase activity increased in parallel with actual osteoblastic induction. Cytokine array assays demonstrated that osteoblastic induction downregulated IL-6 and thrombopoietin, but upregulated IL-8, IL-13, IGF-I and IGFBP-2 in hCP sheets. When differentiated hCP sheets were implanted alone, areas of osteoid and mineralized tissue were formed within 2 weeks, but non-induced, immature hCP sheets did not produce much mineralization. These findings suggest that mature hCP sheets potentially function not only as seeds of ectopic bone formation without the need of synthetic tissue scaffolds, but also as living drug-delivery systems, to influence cells near implantation sites by producing several important cytokines. These two major characteristics indicate that a mature hCP sheet is a promising osteoinductive biomaterial, even without conventional scaffolds for periodontal regenerative therapy.
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PMID:Characterization of human cultured periosteal sheets expressing bone-forming potential: in vitro and in vivo animal studies. 1926 90


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