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)

Tissue injury initiates a cascade of inflammatory mediators and hyperalgesic substances including prostaglandins, cytokines and chemokines. Using microarray and qRT-PCR gene expression analyses, the present study evaluated changes in gene expression of a cascade of cytokines following acute inflammation and the correlation between the changes in the gene expression level and pain intensity in the oral surgery model of tissue injury and acute pain. Tissue injury resulted in a significant upregulation in the gene expression of interleukin-6 (IL-6; 63.3-fold), IL-8 (8.1-fold), chemokine (C-C motif) ligand 2 (CCL2; 8.9-fold), chemokine (C-X-C motif) ligand 1 (CXCL1; 30.5-fold), chemokine (C-X-C motif) ligand 2 (CXCL2; 26-fold) and annexin A1 (ANXA1; 12-fold). The upregulation of IL-6 gene expression was significantly correlated to the upregulation of IL-8, CCL2, CXCL1 and CXCL2 gene expression. Interestingly, the tissue injury-induced upregulation of IL-6, IL-8 and CCL2 gene expression, was positively correlated to pain intensity at 3h post-surgery, the onset of acute inflammatory pain. However, ketorolac treatment did not have a significant effect on the gene expression of IL-6, IL-8, CCL2, CXCL2 and ANXA1 at the same time point of acute inflammation. These results demonstrate that the upregulation of IL-6, IL-8 and CCL2 gene expression contributes to the development of acute inflammation and inflammatory pain. The lack of effect of ketorolac on the expression of these gene products may be related to the ceiling analgesic effects of non-steroidal anti-inflammatory drugs.
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PMID:Upregulation of IL-6, IL-8 and CCL2 gene expression after acute inflammation: Correlation to clinical pain. 1923 64

Placental expression of gonadotropin-releasing hormone (GnRH)-I and II, as well as their cognate receptor, coincides with a period of extensive remodeling of the maternal-fetal interface, near the end of the first trimester of pregnancy. To further define the role of GnRH in human placentation, we performed a microarray screen of HTR-8/SVneo trophoblasts to identify GnRH-regulated genes and their roles in placentation. This screen revealed that GnRH regulates the expression of four angiogenic chemokines: CXCL2, CXCL3, CXCL6, and CXCL8. The microarray data were subsequently confirmed by an extensive Q-PCR time-course analysis. CXCL8, a representative chemokine, was selected for further analysis and shown to be strongly expressed by trophoblasts at the maternal-fetal interface of the human placenta, as well as to accumulate in a GnRH-dependent manner in trophoblast-conditioned media in culture. Trophoblasts were subsequently shown to recruit lymphocytes (Jurkat T cells and primary peripheral blood T and uterine natural killer cells) in chemotaxis assays and this was shown to be GnRH dependent. Furthermore, this recruitment was shown to occur via the release of CXCR1/CXCR2 interacting chemokines, such as the CXCLs investigated in this study. This novel regulation of chemokines by GnRH signaling demonstrates the role of GnRH in regulating the recruitment of lymphocytes to the decidua and the possibility of a direct effect on spiral artery remodeling via the release of proangiogenic chemokines and secondary effects via release of angiogenic factors by recruited lymphocytes.
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PMID:Gonadotropin-releasing hormone-regulated chemokine expression in human placentation. 1943 27

Chemokines are important in inflammation and in carcinogenesis. We hypothesized that besides oro-laryngeal cancer, oral inflammatory states, such as periodontitis, may also influence the chemokine profile of oral fluid. The aim of this study was to characterize the chemokine isoforms in the oral fluid of patients with periodontitis and in the oral fluid of patients with head and neck cancer. Using enzyme-linked immunosorbent assays (ELISA), it was found that the concentrations of CXCL8, CXCL10, and CCL14 were significantly elevated in the oral fluids of the cancer patients. However, periodontitis did not significantly alter the chemokine levels in oral fluid. Identification of chemokine isoforms by a proteomic approach using a newly developed three-step purification procedure was applied on the oral fluid of head and neck cancer and periodontitis patients and on the conditioned medium from carcinoma cells. Carcinoma cells produced predominantly intact CXCL1, CXCL2, CXCL8, and CCL2, whereas CXCL8 also appeared in a truncated, more active, form. Unfortunately, the chemokine concentrations in oral fluids were too low to allow full biochemical identification of the modified isoforms. However, the chemokine profile of head and neck cancer significantly changed after therapy, indicating that it is a useful parameter in clinical practice.
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PMID:Carcinoma cell-derived chemokines and their presence in oral fluid. 1962 45

Cerebral malaria is a severe multifactorial condition associated with the interaction of high numbers of infected erythrocytes to human brain endothelium without invasion into the brain. The result is coma and seizures with death in more than 20% of cases. Because the brain endothelium is at the interface of these processes, we investigated the global gene responses of human brain endothelium after the interaction with Plasmodium falciparum-infected erythrocytes with either high- or low-binding phenotypes. The most significantly up-regulated transcripts were found in gene ontology groups comprising the immune response, apoptosis and antiapoptosis, inflammatory response, cell-cell signaling, and signal transduction and nuclear factor kappaB (NF-kappaB) activation cascade. The proinflammatory NF-kappaB pathway was central to the regulation of the P falciparum-modulated endothelium transcriptome. The proinflammatory molecules, for example, CCL20, CXCL1, CXCL2, IL-6, and IL-8, were increased more than 100-fold, suggesting an important role of blood-brain barrier (BBB) endothelium in the innate defense during P falciparum-infected erythrocyte (Pf-IRBC) sequestration. However, some of these diffusible molecules could have reversible effects on brain tissue and thus on neurologic function. The inflammatory pathways were validated by direct measurement of proteins in brain endothelial supernatants. This study delineates the strong inflammatory component of human brain endothelium contributing to cerebral malaria.
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PMID:Plasmodium falciparum-infected erythrocytes induce NF-kappaB regulated inflammatory pathways in human cerebral endothelium. 1971 60

Gene expression profiles were examined using cDNA microarray technology in human thyroid epithelial (Htori-3) cells exposed to a low, non-toxic dose (10 cGy) of radiation from HZE particles in the form of iron ions in the absence or presence of selenomethionine (SeM). A total of 215 genes were differentially regulated 2 h after exposure to a 10-cGy dose of iron-ion radiation. In the microarray analysis, SeM had profound effects on the radiation-induced expression of several specific genes, which includes PLAU, IGFBP3, FOLR1, B4GALT1 and COL1A1. Of particular interest to us was a gene cluster, "secreted proteins", that was up-regulated after radiation exposure. Seven up-regulated genes of this gene cluster fall within the chemokine/cytokine gene cluster, namely, CXCL1, CXCL2, IL6, IL11, IL8, IL24 and TGFbeta2. In microarray studies, the radiation-induced up-regulated expression of some these genes encoding cytokine/chemokine proteins was significantly decreased by SeM treatment. For IL8, TGFbeta2, CXCL1 and CXCL2, these observations were validated by qPCR techniques. It is concluded that SeM can regulate ionizing radiation-induced gene expression and may serve as an effective countermeasure for some of the acute inflammatory/immune responses induced by low-dose HZE-particle radiation.
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PMID:Induction of cytokine gene expression in human thyroid epithelial cells irradiated with HZE particles (iron ions). 1977 64

Chemokines and their receptors have crucial roles in the trafficking of leukocytes, and are of particular interest in the context of the unique immune responses elicited in the central nervous system (CNS). The chemokine system CC ligand 2 (CCL2) with its receptor CC receptor 2 (CCR2), as well as the receptor CXCR2 and its multiple ligands CXCL1, CXCL2 and CXCL8, have been implicated in a wide range of neuropathologies, including trauma, ischemic injury and multiple sclerosis. This review aims to overview the current understanding of chemokines as mediators of leukocyte migration into the CNS under neuroinflammatory conditions. We will specifically focus on the involvement of two chemokine networks, namely CCL2/CCR2 and CXCL8/CXCR2, in promoting macrophage and neutrophil infiltration, respectively, into the lesioned parenchyma after focal traumatic brain injury. The constitutive brain expression of these chemokines and their receptors, including their recently identified roles in the modulation of neuroprotection, neurogenesis, and neurotransmission, will be discussed. In conclusion, the value of evidence obtained from the use of Ccl2- and Cxcr2-deficient mice will be reported, in the context of potential therapeutics inhibiting chemokine activity which are currently in clinical trial for various inflammatory diseases.
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PMID:Role of chemokines in CNS health and pathology: a focus on the CCL2/CCR2 and CXCL8/CXCR2 networks. 1990 83

Th17 cells are a recently described subset of T helper lymphocytes characterized by the production of IL-17 (IL-17A). Since their discovery in 2003, studies on Th17 cells have become increasingly popular among immunologists and they have emerged as key players in the pathogenesis of multiple sclerosis (MS) and other autoimmune disorders traditionally attributed to Th1 cells. Murine Th17 lymphocytes differentiate from naive CD4+ cells in a specific cytokine environment, which includes TGF-b and IL-6 or IL-21, whereas human Th17 cell development requires TGF-beta, IL-1b, and IL-2 in combination with IL-6, IL-21, or IL-23. Th17-related response is additionally enhanced by osteopontin, TNFalpha, and PGE2 and suppressed by IL-25, IL-27, IL-35, and IL-10. Apart from their main cytokine, Th17 cells can also express IL-17F, IL-21,IL-22, TNFalpha, CCL20, and, in humans, IL-26. All of these mediators may contribute to the proinflammatory action of Th17 cells both in the clearance of various pathogens and in autoimmunity. At least some of these functions are exerted through the induction of neutrophil-recruiting chemokines (CXCL1, CXCL2, CXCL8) by IL-17. Accumulating evidence from studies on mice and humans indicates an important role of Th17 cells in mediating autoimmune neuroinflammation. This has led some immunologists to question the previously exhibited importance of Th1 cells in MS pathology. However, more recent data suggest that both these T-cell subsets are capable of inducing and promoting the disease. Further investigation is required to clarify the role of Th17 cells in the pathogenesis of MS since some of the Th17-related molecules appear as attractive targets for future therapeutic strategies.
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PMID:[Th17 cells in the pathogenesis of multiple sclerosis]. 1994 Mar 28

Rapid translocation of P-selectin from WPB to the surface of endothelial cells is crucial for early neutrophil recruitment to acute inflammatory lesions. Likewise, the chemokine CXCL8/IL-8 is sorted to WPB in human endothelial cells, but little is known about its functional importance in lack of a suitable animal model. Here, we explored the distribution of the functional IL-8 homologues CXCL1/KC, CXCL2/MIP-2, and CXCL5-6/LIX in resting and inflamed murine vessels by confocal microscopy and paired immunostaining with markers of WPB, discovering that these chemokines did not localize to WPB but displayed a granular pattern in a subset of vessels in healthy skin compatible with sorting to the type 2 endothelial compartment for regulated secretion. Moreover, all chemokines colocalized with VWF and P-selectin in platelets, suggesting that their storage in platelet alpha-granules might represent an alternative source of rapidly available, neutrophil-recruiting chemokines. In conclusion, WPB appear not to be involved in regulated secretion of chemokines in the mouse, and instead, the possible existence of type 2 granules and the role of platelets in rapid leukocyte adhesion deserve further attention.
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PMID:The murine IL-8 homologues KC, MIP-2, and LIX are found in endothelial cytoplasmic granules but not in Weibel-Palade bodies. 2000 47

Large DNA viruses, such as herpesvirus and poxvirus, encode proteins that target and exploit the chemokine system of their host. UL146 and UL147 in the cytomegalovirus (CMV) genome encode the two CXC chemokines vCXCL1 and vCXCL2. In this study, vCXCL1 was probed against a panel of the 18 classified human chemokine receptors. In calcium mobilization assays vCXCL1 acted as an agonist on both CXCR1 and CXCR2 but did not activate or block any of the other 16 chemokine receptors. vCXCL1 was characterized and compared with CXCL1/GROalpha, CXCL2/GRObeta, CXCL3/GROgamma, CXCL5/ENA-78, CXCL6/GCP-2, CXCL7/NAP-2 and CXCL8/IL-8 in competition binding, calcium mobilization, inositol triphosphate turnover, and chemotaxis assays using CXCR1- and CXCR2-expressing Chinese hamster ovary, 300.19, COS7, and L1.2 cells. The affinities of vCXCL1 for the CXCR1 and CXCR2 receptors were 44 and 5.6 nm, respectively, as determined in competition binding against radioactively labeled CXCL8. In calcium mobilization, phosphatidylinositol turnover, and chemotaxis assays, vCXCL1 acted as a highly efficacious activator of both receptors, with a rather low potency for the CXCR1 receptor but comparable with CXCL5 and CXCL7. It is suggested that CMV uses the UL146 gene product expressed in infected endothelial cells to attract neutrophils by activating their CXCR1 and CXCR2 receptors, whereby neutrophils can act as carriers of the virus to uninfected endothelial cells. In that way a lasting pool of CMV-infected endothelial cells could be maintained.
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PMID:The cytomegalovirus UL146 gene product vCXCL1 targets both CXCR1 and CXCR2 as an agonist. 2004 80

Inhalation is an important route of cadmium (Cd) exposure, and the lung is considered to be one of the main target organs of Cd toxicity. Pulmonary inflammation seems to be involved in development of many lung diseases. In the present study we show that Cd(2+) at fairly low concentrations affects gene expression of several different cytokines/chemokines in human M1 fibroblasts. The chemokines CXCL2, CXCL3, IL-8/CXCL8 and CCL26, the pro-inflammatory cytokine IL-6 and the receptor IL-1RL1 were expressed at high levels after exposure to 7 microM Cd(2+) for 7h. The expression of some important cytokines was further studied in two different primary cell cultures from rat lungs. Cd(2+) induced cytokine responses at low concentrations (3-6 microM) and early time-points both in type 2 epithelial cell-enriched cultures and alveolar macrophages. However, the two primary lung cells displayed different patterns of cytokine release. Cd(2+) induced an increased release of IL-6 and MIP-2/CXCL2 from the epithelial cells and MIP-2, IL-1beta and TNF-alpha from alveolar macrophages. In conclusion, the marked up-regulation of different cytokines in these cell types, that are important in development of lung injury and disease, suggests that inflammation may contribute in Cd-induced lung damage.
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PMID:Cadmium-induced inflammatory responses in cells relevant for lung toxicity: Expression and release of cytokines in fibroblasts, epithelial cells and macrophages. 2010 57


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