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)

Three highly homologous serine protease inhibitors, SPI-1, SPI-2 and SPI-3 (contrapsins), are synthesized in rat liver. Their expression is regulated differently in healthy and inflamed animals. We found that interleukin 6 (IL-6), a major acute phase cytokine, and to a lesser extent leukemia inhibitory factor (LIF), both together with glucocorticoids, are responsible for the regulation of expression of the contrapsins in rat hepatocytes in primary culture. The effect of IL-6 is time- and dose-dependent. IL-1, TGF beta 1, HGF, PMA and IL-8 did not have any effect on contrapsin mRNA levels. We postulate that SPI-1, SPI-2 and SPI-3 belong to the class II acute phase proteins. Additionally, we show induction of SPI-3 mRNA in rat liver by in situ hybridization using a specific oligonucleotide probe.
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PMID:Rat contrapsins are the type II acute phase proteins: regulation by interleukin 6 on the mRNA level. 751 32

Selective eosinophil recruitment occurs after experimental Ag challenge and in tissue sites of allergic diseases. The mechanisms of selective eosinophil migration are still unknown. In our study, we examined the ability of chemokines to induce transendothelial migration (TEM) of eosinophils in vitro. Among the chemokines tested, only RANTES induced eosinophil TEM. RANTES failed to induce TEM of neutrophils. Interestingly, IL-8 induced neutrophil TEM and had no effect on eosinophil TEM. RANTES-induced TEM was concentration-dependent and was inhibited by Abs directed against the beta 2 integrin CD18. When IL-1-activated endothelial cells were utilized, RANTES-induced TEM also involved the eosinophil beta 1 integrin VLA-4. RANTES did not increase eosinophil adhesion to either resting or IL-1-activated endothelial cells, nor did the chemokine increase CD11b or decrease L-selectin expression. A gradient of RANTES appears to be required for eosinophil TEM. Pre-exposure of eosinophils to IL-5 dramatically potentiated the TEM response to RANTES. These findings suggest that the chemokine RANTES is a potent and selective inducer of eosinophil TEM. Because RANTES appears to be produced in vivo during allergic reactions or in allergic diseases, we speculate that these findings may have some direct relevance to the mechanism of selective eosinophil recruitment in vivo in humans.
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PMID:Eosinophil transendothelial migration induced by cytokines. III. Effect of the chemokine RANTES. 751 42

T cell locomotion within the extracellular matrix may be mediated by cell adhesion molecules. We investigated the expression and function of beta 1- and beta 2-integrins and CD44 on human peripheral CD4+ and CD8+ lymphocytes locomoting in a 3-D type I collagen matrix. Paths of randomly selected T cells were digitized from time-lapse videorecordings and were quantitatively analyzed. After the blocking of CD49b with mAb Gi9, the locomotion of a defined locomotor subset (50% of spontaneously locomoting cells) was inhibited. Anti-CD49d mAb HP2/1 and an activating anti-CD44 mAb (J173), respectively, induced transient recruitment (< 1 h) of previously nonmotile cells (10 to 35%). In contrast to the J173-induced short-term locomotion, hyaluronan incorporated within the matrix promoted locomotion for > 2 h. No significant effects were present for anti-CD49f (GoH3) and -CD11a (25.3) mAbs. After the addition of IL-8 to the matrix, rapid induction of locomotion in 20 to 30% of the cells (control) was evident, which was virtually abolished by anti-alpha 2- and alpha 6-integrin, and -CD11a mAbs. Thus, the locomotion of nonactivated and IL-8-activated T cells may involve different sets of integrins. Using flow cytometry, the development of a CD49b+CD29highCD44lowL-selectinlow T cell phenotype independent of activation markers including CD25, CD27, CD28, VLA-4, and CD45RA- to CD45RO-transition was observed after 4 days in the matrix. The initial development of spontaneous locomotion in the collagen matrix, however, was not accompanied by alterations in CAM surface staining and, therefore, may involve functional CAM activation rather than involving an increase in surface expression.
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PMID:T lymphocyte locomotion in a three-dimensional collagen matrix. Expression and function of cell adhesion molecules. 753 96

Polymorphonuclear leukocytes (PMNL) accumulate in joint fluid in inflammatory arthritides. We investigated the molecular mechanisms required for PMNL migration through a barrier of human synovial fibroblasts (HSF) grown on microporous filters, as a model of PMNL migration through synovial connective tissue and compared this process with PMNL migration through human dermal fibroblast (HDF) barriers and through human umbilical vein endothelium (HUVE). A small amount of PMNL migration occurred spontaneously only through the synovial fibroblast/filter unit (6-10%). Migration markedly increased through all cell monolayers when the chemotactic factors C5a, IL-8, or zymosan-activated plasma (containing C5adesArg) were added to form a chemotactic gradient. The migration induced by C5a, IL-8, or C5adesArg across HSF was partially inhibited (25-76% depending on stimulus) by mAb to CD18 (beta 2 integrin). The CD18-independent migration induced by IL-8 or C5adesArg was almost completely inhibited by mAbs to beta 1 integrin, but with C5a, inhibition by mAb to beta 1 integrin was only partial (40-50%). Inhibition by mAb to beta 1 integrin required treatment of the PMNL, but not the HSF and was only observed when the function of CD11/CD18 on PMNL was also blocked by a mAb. Treatment of PMNL with mAb to alpha 5 (VLA-5) plus alpha 6 (VLA-6) in combination, was required to inhibit CD18-independent migration through HSF to the degree observed with mAb to beta 1 integrin. There was no qualitative difference in the mechanisms utilized by PMNL for migration through HSF or HDF in response to chemotactic factors. In contrast, PMNL migration across HUVE was almost completely CD18-dependent (85%) with no role for beta 1 integrins. The results suggest that (a) PMNL migration through HSF in response to chemotactic factors utilizes both CD11/CD18 and beta 1 (CD29) integrins; (b) the VLA-5 and VLA-6 members of beta 1 integrins are involved in mediating migration; and (c) PMNL utilize similar mechanisms for migration through HSF and HDF, which are distinct from migration through HUVE.
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PMID:Migration of human polymorphonuclear leukocytes through a synovial fibroblast barrier is mediated by both beta 2 (CD11/CD18) integrins and the beta 1 (CD29) integrins VLA-5 and VLA-6. 754 23

It is generally accepted that the beta 2-integrin is restricted to mononuclear leukocytes. The objective of this study was to determine whether neutrophils can also express beta 1-integrin (specifically alpha 4 beta 1) and whether this can support neutrophil adhesion to endothelial cells and to extracellular matrix. We stimulated neutrophils with dihydrocytochalasin B (DHCB) and various chemotactic stimuli and observed that chemotactic stimuli induced neutrophil adhesion via beta 2-integrin (CD18), whereas DHCB and either fMLP, PAF, or IL-8 induced adhesion to endothelium or protein-coated plastic that was not inhibitable by anti-CD18 antibody. beta 2-integrin-deficient cells, which did not respond to chemotactic stimuli alone, also adhered avidly in the presence of chemotactic stimuli and DHCB. The induced neutrophil adhesion was inhibited by antibody to beta 1- or alpha 4-integrin chains, but only if an anti-beta 2-integrin antibody was also present. Flow cytometry revealed increased expression of both beta 1 and alpha 4 in the presence of fMLP plus DHCB. Transendothelial migration of neutrophils induced by chemotactic stimuli alone also increased expression of beta 1 and alpha 4. Transmigration across deendothelialized membranes induced a similar beta 1 expression on neutrophils suggesting that events other than an endothelial signal elicited beta 1-integrin expression. Transmigration-induced beta 1-dependent expression translated into only modest adhesion to protein-coated plastic. These data suggest that both a pharmacological (DHCB) and a physiological (transmigration) stimulus can invoke expression of alpha 4 and beta 1 on human neutrophils to mediate adhesion.
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PMID:A novel beta 1-dependent adhesion pathway on neutrophils: a mechanism invoked by dihydrocytochalasin B or endothelial transmigration. 754 10

Monocytes and polymorphonuclear leukocytes (PMNLs) migrate across cytokine (interleukin-1, tumor necrosis factor) activated endothelium or unstimulated endothelium in response to chemotactic factors in vitro and in vivo utilizing the CD11/CD18 (i.e., beta 2 integrin) adhesion molecule complex. However, in vivo studies have suggested that under some conditions and/or in certain tissues, leukocyte migration can also proceed via CD11/CD18-independent mechanisms. Here we compared adhesion mechanisms involved in the migration of 51Cr-labeled blood monocytes and PMNLs across human umbilical vein endothelium (HUVE) monolayers. We observed that monocyte transendothelial migration was not inhibited by monoclonal antibody (mAb) to CD18, when the HUVE was activated with IL-1 and the chemotactic factor C5a induced the migration. This CD18-independent monocyte migration was blocked by treatment of the monocyte with mAb to beta 1 or alpha 4 integrin, suggesting that very late activation antigen 4 (VLA-4) on the monocyte served as the alternative migration mechanism. In contrast to monocytes, mAb to CD18 inhibited PMNL migration to C5a across IL-1-activated HUVE, but only by 66%, significantly less than with C5a alone (84%) or IL-1-activated HUVE alone (95%). The migration of anti-CD18 mAb-treated PMNLs was not inhibited by function-blocking mAbs to sialyl Lewisx, L-selectin, beta 1 or alpha 4 integrin, the beta 3-related leukocyte response integrin, IL-8, or platelet-activating factor (PAF) antagonists, alone or in combination. Antibody-blocking studies of the ligands on HUVE indicated that E-selectin may be partially involved in this CD18-independent PMNL migration but that ICAM-1, VCAM-1, PECAM-1, and P-selectin are not involved. Of several chemotactic factors tested, C5a and C5adesArg in activated plasma were the most active in inducing CD18-independent migration of PMNLs across IL-1-activated HUVE. These results demonstrate that (1) monocytes can utilize VLA-4 for optimal transendothelial migration and (2) PMNLs may have a novel CD18-independent migration mechanism that is activated by C5a in conjunction with one or more ligands on cytokine-activated endothelium. This may involve, in part, E-selectin interacting with a yet to be identified counterreceptor on PMNLs.
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PMID:CD11/CD18-independent transendothelial migration of human polymorphonuclear leukocytes and monocytes: involvement of distinct and unique mechanisms. 772 14

Macrophages maintain an essential role in orchestrating the host inflammatory response by selectively mobilizing portions of their large secretory repertoire in response to phagocytic as well as other stimuli. For example, after exposure to the inflammatory particulate stimulus zymosan (or its derivative beta 1,3-glucan), monocyte/macrophages synthesize and release lysosomal hydrolases, mobilize arachadonic acid, and secrete cytokines such as TNF-alpha and IL-8. However, the mechanisms by which particulate stimuli promote the selective synthesis and release of macrophage-derived inflammatory gene products are unknown. Given the previously reported potential of transforming growth factor-beta (TGF-beta) as an important mediator of the inflammatory response in vivo, we investigated the role of TGF-beta in the regulation of particulate-induced macrophage inflammatory gene expression. We determined that TGF-beta primed macrophages to synthesize lysosomal hydrolases and express platelet-derived growth factor-B mRNA transcripts in response to both submaximal doses of beta 1,3-glucan and the nonspecific phagocytic stimulus latex particles, which by themselves did not induce expression of either inflammatory gene product. The endogenous production of active TGF-beta was shown to regulate inflammatory gene expression by demonstrating that: 1) beta 1,3-glucan stimulated both TGF-beta mRNA expression and protein release into conditioned media; 2) supernatants from stimulated macrophages primed for lysosomal hydrolase synthesis, and this effect was blocked by anti-TGF-beta antibodies; and 3) anti-TGF-antibodies blocked beta 1,3-glucan-stimulated lysosomal hydrolase synthesis. Collectively, these data describe a novel function for TGF-beta as a priming agent for macrophage inflammatory gene expression and suggest a mechanism for local amplification of the inflammatory response.
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PMID:Transforming growth factor-beta primes macrophages to express inflammatory gene products in response to particulate stimuli by an autocrine/paracrine mechanism. 833 23

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

In 10 patients with Helicobacter pylori (HP) positive chronic gastritis, gastric mucosal content of interleukin (IL)-1 beta, IL-8, Transforming Growth Factor (TGF)-beta 1, Epidermal Growth Factor (EGF) and Polyamines (putrescine, spermine and spermidine) was evaluated before and after eradicating treatment. Histologically, in all patients eradication of HP was accompanied by a marked reduction of the inflammatory infiltrate. At the same time, at the end of the therapeutical regimen, elevated levels of IL-1 beta, IL-8, TGF-beta 1, putrescine and spermidine/spermine ratio significantly dropped, while EGF mucosal content, significantly increased. Results are discussed in terms of the reciprocal role of inflammatory cytokines, growth factors and polyamines in the evolution of the HP-associated chronic gastritis.
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PMID:Successful eradicating treatment of Helicobacter pylori in patients with chronic gastritis: gastric levels of cytokines, epidermal growth factor and polyamines before and after therapy. 868 31

The expression of cytokine transcripts has been investigated in a series of cultured human meningiomas using reverse transcriptase linked polymerase chain reaction (RT-PCR), which allowed simultaneous analysis of a range of cytokines. The main histological subgroups of meningioma were investigated; these included transitional, fibroblastic, and syncytial as well as atypical meningiomas. Meningiomas from each of the different histological subgroups were subjected to a standard tissue culture regime. Total RNA was extracted from representative cultures and reverse-transcribed to yield cDNA. PCR was performed using oligonucleotide primers designed to detect interleukin (IL)-1 alpha/beta to IL-8, transforming growth factor (TGF)beta 1-3, tumour necrosis factor (TNF)alpha/beta, and interferon (IFN)gamma. Transcripts for IL-3, IL-6, IL-8, and TGF beta 3 were detected in all cultures. Transcripts for the three isomers of TGF beta were expressed in the transitional and fibroblastic meningioma cells. TGF beta 2 and TGF beta 3 transcripts were expressed in the syncytial and TGF beta 1 and TGF beta 3 in the atypical meningioma cells. IL-1 beta transcripts were expressed in fibroblastic and atypical cultures and TNF beta transcripts were expressed in syncytial and transitional cultures only. Transcripts for IL-1 alpha, IL-2, IL-4, IL-5, IL-7, TNF alpha, or IFN gamma were not detected in any of the meningioma cultures. This investigation using cells cultured from a small number of tumours from each of the classic histological subtypes suggests that there is a distinct pattern of cytokine mRNA expression linked with histological classification.
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PMID:RT-PCR detection of cytokine transcripts in a series of cultured human meningiomas. 912 Jul 36


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