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)

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.
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PMID:In situ hybridization analysis of cytokine, proto-oncogene and tumour suppressor gene expression in psoriasis. 821 83

We investigated the expression of cytokine transcripts in osteoblast-like cells derived from explants of pagetic and normal bone. A reverse transcription-linked PCR was used that allowed the simultaneous analysis of a range of cytokines. Normal osteoblast-like cells were found to contain the transcripts for IL-1 beta, IL-6, and TGF-beta 1. For the first time we detected in bone cells the two other mammalian isoforms of TGF-beta, beta 2, and beta 3. Furthermore, we have also identified mRNA for IL-3 and the novel chemotactic factor, IL-8. Using this sensitive technique it was not possible to detect mRNA for IL-1 alpha, IL-2, IL-4, IL-5, IL-7, TNF-alpha, or interferon-gamma. The human osteosarcoma cell line Saos-2 also showed a similar pattern of expression of these cytokines to primary osteoblast-like cells, with the exception that TNF-alpha was also identified. Cells isolated from pagetic bone showed essentially the same profile of cytokine expression as normal bone except that TNF-alpha was also detected in two of four samples. The cytokine profile of successive populations of cells harvested from one explant culture at 9, 22, and 57 days showed a consistent pattern of cytokine expression, demonstrating the phenotypic stability of the osteoblast-like cells in long-term cultures.
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PMID:PCR detection of cytokines in normal human and pagetic osteoblast-like cells. 825 52

A number of different cytokines, including IL-1 alpha and beta, IL-2, IL-3, IL-4, IL-6, IL-7, IL-8, IFN-alpha, -beta and gamma, TNF-alpha -beta, and TGF-beta 1, can modulate the expression of distinct cell surface antigens of normal and neoplastic cells. Both induction/increase of expression and reduction of expression can be achieved depending on the antigen and on the cytokine. Antigens subjected to the modulating activity of cytokines include distinct families of cell surface structures such as the molecules coded by the major histocompatibility complex (MHC), the superfamily of adhesion receptors that regulate cell-cell and cell-matrix interaction, receptors for cytokines and growth factors and tumor-associated antigens. The modulating activity of cytokines is a consequence of their influence on gene expression, protein synthesis, membrane expression and shedding of antigens from the cell surface. The changes of phenotype due to the action of cytokines can influence the signalling pathways dependent on the expression and function of cell surface structures. Therefore, the antigen modulating activity of cytokines can thoroughly affect the biological behavior of normal and neoplastic cells. As described here, most of the modulating effects of cytokines on different cell surface structures and the functional consequences of antigenic modulation can be verified in human malignant melanoma cells.
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PMID:The role of cytokines in the modulation of cell surface antigens of human melanoma. 827 6

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.
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PMID:IL-8 produced by human malignant melanoma cells in vitro is an essential autocrine growth factor. 808 4

Hyperplasia of mesangial cells (MCs) precedes or accompanies progressive glomerular scarring, as is seen in chronic glomerulonephritis and diabetic glomerulosclerosis. The mechanisms causing in vivo MC proliferation and production of extracellular matrix (ECM) are incompletely understood. Cell culture studies have demonstrated that MCs produce as well as react to various polypeptide cytokines. Thus, MCs have the potential to generate soluble mediators which can, in a paracrine fashion, attract and activate inflammatory cells (platelets, monocyte-macrophages, granulocytes), for example by IL-6, IL-8, MCP-1 and GM-CSF, and exert autocrine effects on MCs themselves, such as by promoting MC proliferation (by PDGF, IL-1, IL-6) or ECM production (by TGF-beta, IL-1). Recent in vitro results have revealed that specific non-soluble ECM components (collagen III, IV; laminin) also affect MC behavior with regard to adhesion, cell replication, ECM production as well as their response to cytokines. The latter effect appears to be mediated by alterations of cytokine receptor expression on MCs in the presence of the ECM components. "Cross-talk" between MCs, cytokines, ECM and inflammatory cells is likely to be of great importance in the regulation of the MC phenotype and may play a prominent role in the initiation and progression of glomerular inflammation. First in vivo findings in rats with experimental glomerular disease and in kidney biopsies from patients with glomerulonephritis have supported this concept by demonstrating abnormal MC expression of cytokines, their receptors and ECM proteins. These MC products may promote the recruitment and activation of inflammatory cells and perpetuate MC proliferation as well as ECM build-up.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokines and mesangial cells. 846 21

Acute inflammatory reactions are usually characterized by polymorphonuclear leucocyte (PMNL) migration into inflamed tissues. Transforming growth factors-beta 1 (TGF-beta 1) may be involved in inflammatory reactions but its actions are controversial and require further in vivo studies. We employed a rabbit dermal inflammation model to investigate the effect of TGF-beta 1 on PMNL migration induced by cytokines and chemotactic factors, using 51Cr-labelled leucocytes to quantify PMNL accumulation in dermal lesions. Injection of TGF-beta 1, over a wide dose range, alone did not elicit PMNL accumulation (0.14 x 10(6) PMNL/site). This contrasted with responses to interleukin-1 alpha (IL-1 alpha) (11.8 x 10(6) PMNL/site), tumour necrosis factor-alpha (TNF-alpha) (4.5), lipopolysaccharide (LPS) (14.9), FNLP (10.1), or IL-8 (6.6). However, when sites were pretreated for 3 hr with TGF-beta 1 (1-10 ng) and subsequently re-injected with the inflammatory stimuli, TGF-beta 1 primed the tissue for an enhanced recruitment of PMNL in response to the endothelium-activating inflammatory agents, IL-1 alpha, TNF-alpha and LPS, but not to IL-8 or FNLP, which are directly PMNL chemotactic. For example, with IL-1 alpha, PMNL accumulation was 205% greater than the additive sum of each response alone (P < 0.05). This was confirmed histologically. TGF-beta 1 pretreatment enhanced PMNL accumulation over a wide dose range of IL-1 alpha and LPS. TGF-beta 1 did not alter the kinetics of IL-1 alpha or LPS-induced PMNL accumulation, but increased the peak rate of accumulation in lesions. Using an in vitro PMNL transendothelial migration system, TGF-beta 1 (10 ng/ml) was found to prime the endothelium for responsiveness to a submaximal dose of IL-1 alpha (0.005 ng/ml) or a threshold dose of LPS (0.01 ng/ml), resulting in enhanced PMNL transendothelial migration. Thus, TGF-beta 1 may have a role in priming the microvasculature for enhanced PMNL emigration, especially in response to endothelium-activating agents.
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PMID:Transforming growth factor-beta 1 enhances polymorphonuclear leucocyte accumulation in dermal inflammation and transendothelial migration by a priming action. 847 13

We present a detailed analysis of cytokine expression patterns of the two permanent human bone marrow stromal cell lines, L87/4 and L88/5. These cell lines, previously established in our laboratory, are highly radiotolerant without cell detachment and support long-term cultures of CD(34+)-enriched human cord blood cells. RT-PCR analysis of 22 different cytokines or cytokine receptor mRNAs showed an almost identical expression pattern in the two stromal cell lines compared to primary human Dexter-type stroma. Since stromal feeder lines employed in long-term cultures usually are irradiated and grown in media containing corticosteroids, we analyzed the impact of irradiation and dexamethasone on cytokine production in the two cell lines by RT-PCR, Northern blot analysis, bioassays, and RIAs. By RT-PCR analysis, constitutive mRNA expression of c-kit, G-CSF, GM-CSF, IL-1 beta, IL-6, IL-7, IL-8, IL-11, Kit ligand (KL), LIF, M-CSF, MIP-1 alpha, TGF-beta, and TNF-alpha was demonstrated in both cell lines, with L87/4 a more potent cytokine producer than L88/5. Northern blot data showed an increase in mRNA levels for GM-CSF, IL-1 beta, and LIF by irradiation and IL-1 alpha treatment in both cell lines. IL-1 alpha-induced GM-CSF, IL-1 beta, IL-6, IL-11, and LIF mRNA levels were reduced by the addition of dexamethasone, whereas dexamethasone had no influence on the amounts of IL-1 alpha-induced G-CSF mRNA. L87/4 and, to a lower extent, L88/5 cells showed dexamethasone-dependent increases in KL mRNA, while KL mRNA levels were not stimulated by IL-1 alpha.
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PMID:Constitutive and modulated cytokine expression in two permanent human bone marrow stromal cell lines. 853 85

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.
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PMID:Expression of cytokines and immune mediators during chronic liver allograft rejection. 854 86

Leukocyte recruitment to inflammatory foci is generally associated with cellular activation. Recent evidence suggests that chemotactic agents can be divided into two classes, "classical chemoattractants" such as FMLP, C5a, and IL-8, which stimulate directed migration and activation events and "pure chemoattractants" such as TGF-beta 1 which influence actin polymerisation and movement but not oxidative burst and associated granular enzyme release. The studies reported here demonstrate that the murine S100 chemoattractant protein, CP-10, belongs to the "non-classical" group. Despite its potent chemotactic activity for neutrophils and monocytes/macrophages, CP-10 failed to increase [Ca2+]i in human or mouse PMN, although chemotaxis was inhibited by pertussis toxin, confirming the suggestion of a novel Ca(2+)-independent G-protein-coupled pathway for post-receptor signal transduction triggered by "pure chemoattractants." The co-ordinated up-regulation of Mac-1 and down-regulation of L-selectin induced by FMLP on human PMN in vitro was not observed with CP-10. Quantitative changes in immediate (30 s) actin polymerisation occurred with FMLP and CP-10-treated human PMN. The relative F-actin increases induced in WEHI 265 monocytoid cells by FMLP and CP-10 was optimal at 60 s and declined over 120 s. F-actin changes reflected the concentration and potencies of the agonists required to provoke chemotaxis. After 90 min, CP-10 profoundly altered cell shape and increased both cell size and F-actin within pseudopodia. These changes are typical of those mediating leukocyte deformability, and CP-10 may mediate leukocyte retention within microcapillaries and thereby contribute to the initiation of inflammation in vascular beds.
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PMID:S100 protein CP-10 stimulates myeloid cell chemotaxis without activation. 859 3

To study the capacity and regulation of cytokine production by normal peripheral blood eosinophils, we isolated eosinophils from healthy individuals and stimulated them with immobilized Ig or TNF-alpha, with or without exogenous IL-5. By reverse transcription-PCR, uncultured, freshly isolated eosinophils constitutively expressed mRNA for IL-4, IL-10, and TGF-beta1. Eosinophils stimulated by immobilized secretory IgA, immobilized IgA, immobilized IgG, or TNF-alpha for 3 h expressed mRNA encoding IL-3, IL-4, IL-8, IL-10, granulocyte-macrophage CSF, TNF-alpha, TGF-beta, and RANTES. The mRNA for IL-2, IL-5, or IFN-gamma was not detected. IL-4 and IL-10 protein, but not IL-8, were measurable in lysates of fresh eosinophils or eosinophils cultured with medium alone for 24 h. Eosinophils incubated with immobilized Ig or TNF-alpha released IL-8 protein into the supernatants. In contrast, IL-4 and IL-10 proteins were not detectable. Soluble secretory IgA immune complexes also induced degranulation, as measured by eosinophil-derived neurotoxin, and IL-8 release, but not IL-4 or IL-10 release, from eosinophils. Release of IL-8 protein and storage of IL-4 and IL-10 proteins were enhanced by exogenous IL-5 and inhibited by a transcription inhibitor, actinomycin D. Degranulation of stored granule proteins was not affected by actinomycin D. Therefore, normal peripheral blood eosinophils can transcribe and synthesize several cytokines, including IL-4, IL-8, and IL-10; some are stored, and some are released. These cytokines may play important roles in modulating immune responses in diseases associated with eosinophils.
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PMID:Constitutive production of IL-4 and IL-10 and stimulated production of IL-8 by normal peripheral blood eosinophils. 864 35


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