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)

To our knowledge, this is the first sequential study of cytokines in tissue sections of developing and healing tuberculous (BCG) lesions. In situ hybridization, immunohistochemical, and RT-PCR techniques were used. Cytokine mRNAs showed a biphasic pattern. The percentage of mononuclear cells (MN) containing IL-1beta, TNF-alpha, MCP-1, and IL-8 mRNAs was highest in 1- to 3-day lesions, apparently because of the nonspecific inflammatory response caused by the tubercle bacilli in the BCG vaccine. At 5 days, this percentage was significantly reduced. With IFN-gamma, the peak and trough were delayed by 2 days. By 9 days, the percentage of MN containing the mRNAs of all five cytokines had again increased and the rabbits had become tuberculin-positive. In general, MCP-1 and TNF-alpha proteins and the vascular adhesion molecules, ICAM, VCAM, and perhaps ELAM, peaked at about 3 days. Many mononuclear cells surrounding the central areas of solid and liquefied caseous necrosis contained chemokine IL-8 mRNA. IL-8 is known to attract PMN, and PMN were present nearby. In contrast, MN containing chemokine MCP-1 mRNA were present more peripherally in areas rich in macrophages and lymphocytes. The early nonspecific cytokine response seems to be an adjuvant effect of the mycobacteria in BCG vaccine in that it causes a rapid entry of macrophages, lymphocytes, granulocytes, and probably dendritic cells into local sites of antigen deposition. This effect should be considered in developing improved vaccines for the prevention of tuberculosis, because BCG vaccines producing a strong early cytokine response should be more immunogenic than BCG vaccines with similar antigens producing a weak response.
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PMID:Nonspecific and immune-specific up-regulation of cytokines in rabbit dermal tuberculous (BCG) lesions. 954 73

Leukocytes have been implicated to be involved in the pathogenesis of IgA nephropathy (IgAN). To clarify the precise molecular mechanism of recruitment and activation of leukocytes in the subgroups of IgAN, latent, acute, and chronic types, we studied monocyte chemotactic and activating factor (MCAF/MCP-1) and interleukin (IL)-8 in urines and renal expression of these cytokines. Urinary MCAF levels were significantly higher in chronic type, and were correlated with pathological progressive factors such as mesangial proliferation and interstitial cellular infiltration associated with CD68-positive macrophage. On the other hand, urinary IL-8 elevated only in acute type and were correlated with glomerular endocapillary proliferation and the degree of hematuria. In immunohistochemical study, IL-8 was mainly observed in glomeruli, otherwise MCAF in vascular endothelial cells, tubular epithelial cells, and infiltrated mononuclear cells in the interstitial lesions. These observations demonstrated that MCAF and IL-8 were differentially expressed in kidneys with IgAN, and their subtypes, and suggest that chemokines may be involved in the pathogenesis of IgAN at distinct phases or pathological lesions, possibly through the recruitment and activation of a distinct type of leukocyte.
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PMID:Urinary levels of chemokines (MCAF/MCP-1, IL-8) reflect distinct disease activities and phases of human IgA nephropathy. 954 80

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

The final composition of leukocytes present in a site of inflammation in response to chemokine stimulation and activation may depend on both the nature of the secreted chemokines as well as the relative expression of the multitude of specific chemokine cell surface receptors on many different cell types. Because related receptors with different affinities and cross-reactive binding capabilities are present on each type of leukocyte, relative differences in receptor distribution and receptor affinity for specific chemokines may significantly influence which cells are ultimately attracted to and activated by each individual chemokine. Production of IL-8, MCP-1, and ENA-78 by endothelial cells, LPMNC, and epithelial cells in IBD could establish a chemotactic gradient capable of influencing the increased migration of monocytes/macrophages, granulocytes, and lymphocytes from the blood stream through the endothelium into both the mucosa and submucosa during chronic IBD. The ability of chemokines to induce chemotaxis, leukocyte activation, granule exocytosis, increased production of metalloenzymes, and up-regulation of respiratory burst activity indicates that there may be a variety of different mechanisms by which chemokines could markedly increase chronic inflammation and chronic intestinal tissue destruction in IBD.
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PMID:The central role of chemokines (chemotactic cytokines) in the immunopathogenesis of ulcerative colitis and Crohn's disease. 955 29

Chemokines (chemoattractant cytokines) attract and activate specific leukocyte subsets. With regard to their expression by brain parenchymal cells, they may represent the key molecules that control leukocyte entry into the subarachnoid space. In order to evaluate the contribution of chemokines in vivo, we determined the levels of MCP-1, MIP-1alpha, RANTES, IL-8, as well as of the sIL-2R in three patients with proven herpes simplex encephalitis type 1 (HSE-1). CSF samples were drawn by a subarachnoid catheter system throughout the time course of hospitalisation. Results were compared to chemokine levels in serum drawn in parallel. The clinical status was documented by the Modified Barthel Index and correlated with chemokine levels in the CSF. The results were compared with the chemokine levels in the CSF of 17 control patients with normal CSF routine parameters. High chemokine levels were detectable in the CSF of all HSE-patients. MCP-1 peak levels were found at the time of admission, while maximal IL-8 levels occurred 4 to 8 h later. The levels of MIP-1alpha and RANTES were lower than those of MCP-1 with a maximum at the time of admission. In all patients the levels of the sIL-2R increased later in the time course, at 14 to 20 h after admission. When the levels of MCP-1 were compared with the clinical status by Modified Barthel Index, we found a high reciprocal correlation (r=-0.82). Routine CSF parameters, such as leukocytes, albumin and immunoglobulins did not correlate with the clinical status. Chemokine levels in serum were found to be close to the detection limits of the ELISA systems. Our data suggest that chemokines play an important role in the pathogenesis of HSE. They may be useful parameters to monitor the stage and severity of the disease. The late increase of sIL2-R levels may indicate the beginning of the reconstitution phase.
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PMID:Time course of chemokines in the cerebrospinal fluid and serum during herpes simplex type 1 encephalitis. 960 Jun 81

Rheumatoid arthritis is an autoimmune disease that causes inflammation mainly in synovial tissues. RA manifests as a chronic polyarthritis with intermittent acute inflammatory episodes. The inflammatory sites are characterized by infiltration of activated lymphocytes and macrophages into the synovial membrane, and the proliferation of synovial cells. The local production of a number of cytokines by proliferative synovial cells as well as by infiltrating cells appears to account for many of the pathological and clinical manifestations in rheumatoid arthritis. Tissues were collected from twelve RA patients undergoing joint replacement surgery. The synovium was collected and the cell types were identified, and markers for chronic and acute inflammatory mediators were measured. The cells types found in the synovium are capable of secreting cytokines which are capable of both acute inflammation (IL-1, IL-6, IL-8, MCP-1 and TNF), as well as chronic inflammation (IL-2, IL-10, and IL-4). The results obtained showed that the macrophages-derived acute inflammatory cytokines (IL-1, IL-6 and IL-8) were easily detected at levels of 22.6 +/- 12 pg/mg protein; 48.5 +/- 42 pg/mg protein, and 76 +/- 31 pg/mg protein; respectively. T-cell derived chronic inflammation cytokines (IL-2, IL-4 and IL-10) were rarely detected. Retrieved tissues that immunostained positive for IL-6, IL-1 and IL-8 also is suggestive of an acute inflammatory response. The results clearly demonstrate that the acute response may be responsible for the subsequent need for joint arthroplasties.
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PMID:Synovial tissues collected from rheumatoid patients undergoing total joint arthroplasty express markers for acute inflammation. 960 33

ICAM-3 is expressed at high levels on myeloid leukocytes, but its function on these cells is unknown. We tested the hypothesis that it transduces outside-in proinflammatory signals using immobilized mAbs to engage ICAM-3 on freshly isolated human monocytes and neutrophils. Two immobilized Abs that recognize epitopes in the extracellular domain 1 of ICAM-3, which is critical for recognition by the alphaL/beta2 integrin, potently induced secretion of MIP-1alpha, IL-8, and MCP-1 by monocytes and triggered IL-8 secretion by neutrophils. These chemokines are products of immediate-early genes that are induced when myeloid cells are activated. Chemokine secretion induced by "triggering" Abs was greater than that induced by isotype-matched immobilized Abs against ICAM-1, ICAM-2, PECAM-1, control Igs, or immobilized control proteins. Coengagement of ICAM-3 and Fc receptors (FcgammaRI or FcgammaRII) was required for maximal chemokine secretion by monocytes. Microscopy documented that there is also dramatic spreading of monocytes when surface ICAM-3 is engaged by immobilized Abs. Spreading was induced by Fab and F(ab')2 fragments of triggering anti-ICAM-3 mAb, demonstrating direct outside-in signaling, but was not required for chemokine secretion. These experiments indicate that ICAM-3 may transmit outside-in signals when it is engaged by beta2 integrins during myeloid cell-cell interactions in inflammatory lesions. Binding of Fc receptors by Ig in the local environment can amplify the responses.
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PMID:Coengagement of ICAM-3 and Fc receptors induces chemokine secretion and spreading by myeloid leukocytes. 960 63

Leukocyte accumulation and activation are key events in the pathogenesis of inflammatory lung disease. The ability of human airway smooth muscle cells (HASM) to contribute to the inflammatory process by its ability to produce the chemokines interleukin (IL) 8, monocyte chemotactic protein (MCP-1) and regulated on activation, normal T cell expressed and secreted (RANTES) was investigated. Cultured HASM, when stimulated with the pro-inflammatory cytokines IL-1 alpha (0.01-1 ng/ml) or tumour necrosis factor alpha (TNF-alpha, 0.3-30 ng/ml), synthesize and release substantial amounts of IL-8, as assessed by specific immunoassay, bioasssay (elevation of intracellular free calcium in human neutrophils), and upregulation of mRNA. These stimuli also increased MCP-1 production and mRNA expression, but RANTES mRNA expression was not detected at 24 h. The smooth muscle spasmogen endothelin 1 (1 microM) was unable to stimulate IL-8 or MCP-1 release or mRNA expression. These data indicate that HASM may constitute an important source of leukocyte attractants in the inflamed lung, where the inducing stimuli, IL-1 alpha and TNF-alpha, are also likely to be present.
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PMID:Interleukin 8 and monocyte chemoattractant protein 1 production by cultured human airway smooth muscle cells. 961 72

There is evidence for the presence of lysophosphatidylcholine (lysoPC) in oxidatively modified low density lipoprotein, human plasma and in atherosclerotic lesions. We studied the effect of lysoPC on the cytokine production by human monocytes. Among all the cytokines tested (IL-8, TNF alpha, MCP-1 and IL-1beta), we found that lysoPC most consistently stimulated human monocytes to produce IL-1beta in a dose and time dependent manner. Adherent monocytes were exposed to lysoPC in cell culture medium containing 0.5% bovine serum albumin. When exposed to lysoPC from 12.5 to 75 microM, the cellular content of IL-1beta increased 2-4 fold. Up to a concentration of 50 microM no cytotoxic effect could be seen. Over 50 microM there was evidence of toxicity. The level of IL-1beta reached its highest level at 24 h and then declined. At 48 h, the cell associated IL-1beta was low, but still the lysoPC stimulated cells produced 4.1 times more IL-1beta than controls. Also the IL-1beta mRNA was augmented by lysoPC in parallel with the IL-1beta protein levels. The stimulatory effect of lysoPC was dependent on its chain length. There was no effect on IL-1beta production when the acyl chain was shorter than 16. We also found that saturated lysoPC 18:0 stimulated IL-1beta production more than the monounsaturated lysoPC 18:1. Thus, the lysoPC in oxidatively modified LDL may stimulate the production of IL-1beta in macrophages, which may contribute to the inflammatory response in atherosclerotic tissue.
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PMID:Lysophosphatidylcholine induces the production of IL-1beta by human monocytes. 962 78

Chemokines constitute a constantly growing family of small inflammatory cytokines. They have been implied in many different diseases of the CNS including trauma, stroke and inflammation, e.g., multiple sclerosis. In this review we focus on the role of chemokines in infectious meningitis of bacterial or viral origin. In experimental bacterial meningitis induced by Listeria monocytogeneses both CXC and CC chemokines namely MIP-1alpha, MIP-1beta and MIP-2 are produced intrathecally by meningeal macrophages and leukocytes which infiltrate into the CNS. In patients with bacterial meningitis, IL-8, GROalpha, MCP-1, MIP-1alpha and MIP-1beta are detectable in the CSF. These chemokines contribute to CSF mediated chemotaxis on neutrophils and PBMC in vitro. In viral meningitis IL-8, IP-10 and MCP-1 are identified in the CSF to be responsible for chemotactic activity on neutrophils, PBMC and activated T cells. Taken collectively these data indicate that the recruitment of leukocytes in infectious meningitis involves the intrathecal production of chemokines.
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PMID:Chemokines and chemotaxis of leukocytes in infectious meningitis. 962 95


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