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)

The only curative therapy for sickle cell disease (SCD) is allogeneic hematopoietic stem cell (HSC) transplantation. Gene therapy approaches for autologous HSC transplantation are being developed. Although earlier engraftment is seen when cells from GCSF-mobilized blood are transplanted than when bone marrow is transplanted, administration of GCSF to patients with SCD can cause significant morbidity. We tested whether primitive hematopoietic progenitors are spontaneously mobilized in the blood of patients with SCD during acute crisis (AC-SCD patients). The frequency of myeloid-lymphoid-initiating cells (ML-ICs) and SCID-repopulating cells (SRCs) was significantly higher in blood from AC-SCD patients than in blood from patients with steady-state SCD or from normal donors. The presence of SRCs in peripheral blood was not associated with detection of long-term culture-initiating cells, consistent with the notion that SRCs are more primitive than long-term culture-initiating cells. As ML-ICs and SRCs were both detected in blood of AC-SCD patients only, these assays may both measure primitive progenitors. The frequency of ML-ICs also correlated with increases in stem cell factor, GCSF, and IL-8 levels in AC-SCD compared with steady-state SCD and normal-donor sera. Because significant numbers of ML-ICs and SRCs are mobilized in the blood without exogenous cytokine treatment during acute crisis of SCD, collection of peripheral blood progenitors during crisis may yield a source of autologous HSCs suitable for ex-vivo correction by gene therapy approaches and subsequent transplantation.
 ...
PMID:Spontaneous circulation of myeloid-lymphoid-initiating cells and SCID-repopulating cells in sickle cell crisis. 1263 87

Interleukin 10 (IL10) is a powerful Th-2 cell cytokine produced by lymphoid cells that exerts its functions by inhibiting macrophage/monocyte and T-cell lymphocyte replication and secretion of inflammatory cytokines (IL1, TNFA, TGFB, IL6, IL8 and IL12). Genetic association analysis of a well-characterized HBV cohort revealed that one of IL10 haplotypes, IL10-ht2, was strongly associated with hepatocellular carcinoma (HCC) occurrence in gene dose-dependent manner. The frequency of susceptible IL10-ht2 was much higher in HCC patients and significantly increased in order of susceptibility to HBV progression from chronic hepatitis to liver cirrhosis and HCC among hepatitis B patients. In addition, survival analysis clearly showed that the onset age of HCC was also accelerated among chronic hepatitis B patients who were carrying IL10-ht2. Increased IL10 production mediated by IL10-ht2 suggests that up-regulated IL10 accelerates progression of chronic HBV infection, especially to HCC development.
 ...
PMID:Interleukin 10 haplotype associated with increased risk of hepatocellular carcinoma. 1266 13

The early consequences of Helicobacter pylori infection and the role of bacterial virulence determinants in disease outcome remain to be established. The present study sought to measure the development of host inflammatory and immune responses and their relationship to the putative bacterial virulence factors cag pathogenicity island (cagPAI), vacA allele, and oipA in combination with bacterial colonization density in a feline model of the early stages of H. pylori infection. Gastric tissues obtained from infected and uninfected cats were evaluated for H. pylori ureB, cagPAI, vacA allele, and oipA and colonization density (urease, histology, and real-time PCR). Inflammation was assessed by measuring mRNA upregulation of gamma interferon (IFN-gamma), interleukin (IL)-1 alpha, IL-1 beta, IL-4, IL-6, IL-8, IL-10, and IL-12 p40 and histopathology. The mucosal immune response was characterized by morphometric analysis of lymphoid follicles and by differentiating lymphocyte populations with antibodies against surface markers. Infecting H. pylori strains were positive for vacAs1 but lacked cagPAI and an active oipA gene. Colonization density was uniform throughout the stomach. Upregulation of IFN-gamma, IL-1 alpha, IL-1 beta, and IL-8 and increased severity of inflammatory infiltrates and fibrosis were observed in infected cats. The median number and total area of lymphoid aggregates were 5 and 10 times greater, respectively, in the stomachs of infected than uninfected cats. Secondary lymphoid follicles in uninfected cats were rare and positive for BLA.36 and B220 but negative for CD3 and CD79 alpha, whereas in infected cats they were frequent and positive for BLA.36, CD79 alpha, and CD3 but negative for B220. Upregulation of IFN-gamma, IL-1 alpha, IL-1 beta, and IL-8 and marked hyperplasia of secondary lymphoid follicles are early consequences of H. pylori infection in cats. The response appears to be similar to that of infected people, particularly children, can develop independently of the pathogenicity factors cagPAI and oipA, and is not correlated with the degree of colonization density or urease activity.
 ...
PMID:Quantitative evaluation of inflammatory and immune responses in the early stages of chronic Helicobacter pylori infection. 1270 44

The stomach is an organ which is usually sterile and without lymphoid tissue. Its colonization by Helicobacter pylori leads to an important inflammatory response, gastritis. Polymorphs and macrophages are attracted and activated. Epithelial cells contribute to this innate response by the chemokines produced such as interleukin 8. The reaction observed is of Th1 type, probably inappropriate against an extra-cellular pathogen. The deleterious effect caused by oxygen free radicals is important. Two types of topographic evolution of the gastritis can be observed: antral gastritis which can lead to ulcer disease, and pangastritis which can lead to gastric carcinoma. In addition to host genetic factors, environmental factors and characteristics of the infecting strain can be involved. The maximum risk to develop a gastric cancer occurs for subjects harboring certain alleles of the interleukin 1B and H. pylori strains with the cag pathogenicity island.
 ...
PMID:[Helicobacter pylori, gastric inflammation and its consequences]. 1284 63

Fifteen 8-week-old conventional pigs were selected from a farm where pigs were suffering from postweaning multisystemic wasting syndrome (PMWS). Ten of the animals were diseased pigs showing typical signs of PMWS (wasting and respiratory disorders) and positive for infection with porcine circovirus type 2 (PCV2), and the other five animals selected as controls were pen-mate, apparently healthy pigs. Blood samples and lymphoid tissues were taken from each animal for haematological, serological and histopathological studies. Also, cytokine mRNA expression of IL-1beta, IL-2, IL-4, IL-8, IL-10, IL-12p40 and IFN-gamma from inguinal and bronchial lymph nodes, tonsils, spleen and thymus was determined by semi-quantitative RT-PCR. Pigs suffering from PMWS showed severe alterations of haematological parameters such as anaemia, lymphopenia with decrease of CD8(+) and IgM(+) cells, monocytosis and neutrophilia. Also, extensive lymphocyte depletion and altered cytokine mRNA expression patterns were seen in most of the examined lymphoid organs. Those cytokine mRNA alterations were characterized by an overexpression of IL-10 mRNA in thymus and IFN-gamma mRNA in tonsils, and by decreases in the mRNA expression of several cytokines as IL-2 and IL-12p40 in the spleen, IL-4 in tonsils, and IFN-gamma, IL-10, IL-12p40 and IL-4 in inguinal lymph nodes. Also, the IL-10 mRNA overexpression was histologically associated with the thymic depletion and atrophy observed in PMWS pigs. In conclusion, the cytokine mRNA imbalance, specially the increased mRNA levels of IL-10 in the thymus, jointly with the histopathological and haematological disorders, are highly indicative of a T-cell immunosuppression, enhancing the notion that the immune system of PMWS-affected pigs is severely impaired.
 ...
PMID:Cytokine mRNA expression profiles in lymphoid tissues of pigs naturally affected by postweaning multisystemic wasting syndrome. 1286 43

Vav1 is a hemopoietic-specific Rho/Rac guanine nucleotide exchange factor that plays a prominent role in responses to multisubunit immune recognition receptors in lymphoid cells, but its contribution to regulation of neutrophil functions is unknown. Activated Rho family GTPases are critical participants in neutrophil signaling cascades initiated by binding of FMLP and other chemoattractants to their cognate G protein-coupled receptors. Therefore, we investigated whether Vav1 regulates chemoattractant-induced responses in neutrophils. We found that superoxide production elicited by FMLP in Vav1(-/-) murine neutrophils isolated from either bone marrow or from peritoneal exudates was substantially reduced compared with that of wild type. Filamentous actin generation in FMLP-stimulated Vav1(-/-) neutrophils was also markedly reduced, whereas it was normal in response to IL-8 or leukotriene B(4). FMLP induced tyrosine phosphorylation of Vav1, whereas IL-8 or leukotriene B(4) did not, correlating with the requirement for Vav1 in chemoattractant-stimulated filamentous actin generation. Neutrophil motility in vitro and neutrophil mobilization into peripheral blood in vivo elicited by FMLP were both decreased in Vav1(-/-) mice. Hence, this study defines a new role for Vav1 in regulating granulocytic leukocytes as well as linking Vav1 to specific cellular responses downstream of a seven transmembrane domain receptor.
 ...
PMID:The hemopoietic Rho/Rac guanine nucleotide exchange factor Vav1 regulates N-formyl-methionyl-leucyl-phenylalanine-activated neutrophil functions. 1453 Mar 69

T-cell homing within germinal centres (GCs) is required for humoral B-cell responses. However, the mechanisms implicated in the recruitment of T cells into the GC are not completely understood. Here we show, by immunohistology, and Northern and Western blots, that in vivo human GC B lymphocytes can express CxC and CC chemokines. Moreover, B-cell subset-specific experiments reveal that interleukin (IL)-8 and regulated on activation, normal, T-cell expressed, and secreted (RANTES) are predominantly expressed by GC centroblast and centrocytes, suggesting that chemokine expression is essential at stages in which B-lymphocytes engage in active antigen-dependent interactions with T lymphocytes. In keeping with this hypothesis, we show that the T cells recruited into the GC correlatively express the receptors for IL-8 and RANTES. We propose that chemokine expression is a key B-cell function that facilitates T-lymphocyte recruitment into the GCs and supports cognate B-cell : T-cell encounters. Moreover, our data are consistent with the impaired homing of T cells to secondary lymphoid organs in mice that are either deficient in CC and CxC chemokines or their receptors.
 ...
PMID:In vivo expression of interleukin-8, and regulated on activation, normal, T-cell expressed, and secreted, by human germinal centre B lymphocytes. 1463 56

The selective accumulation of different leucocyte populations during inflammation is regulated by adhesion molecules and chemokines expressed by vascular endothelium. This study examined how chemokine production and the expression of adhesion molecules and chemokine receptors vary between endothelia from different vascular beds. Human saphenous vein endothelium was compared with lung and dermal microvascular endothelia and with umbilical vein endothelium and a bone-marrow endothelial cell line. All endothelia produced CCL2 and CXCL8 constitutively, whereas CXCL10 and CCL5 were only secreted after tumour necrosis factor (TNF)-alpha or interferon (IFN)-gamma stimulation. In combination with TNF-alpha, IFN-gamma suppressed CXCL8 but enhanced CCL5 and CXCL10, whereas transforming growth factor (TGF)-beta reduced secretion of all chemokines. Basal chemokine secretion was higher from umbilical vein than other endothelial cells. Chemokine receptors, CXCR1, CXCR3 and CCR3, were present on all endothelia but highest on saphenous vein. CCR4, CCR5, CCR6, CXCR2, CXCR4 and CXCR5 were also detected at variable levels on different endothelia. The variation between endothelia in chemokine secretion was much greater than the variations in adhesion molecules, both on resting cells and following cytokine stimulation. These results indicate that it is the tissue-specific variations in endothelial chemokine secretion rather than variations in adhesion molecules that can explain the different patterns of inflammation and leucocyte traffic seen in non-lymphoid tissues.
 ...
PMID:Chemokines, chemokine receptors and adhesion molecules on different human endothelia: discriminating the tissue-specific functions that affect leucocyte migration. 1463 48

Host immunity, particularly T cell immunity (Th1/Th2 balance), plays an important role in clinicopathological features of malignant disease. However, the T cell immunity has not been fully investigated in patients with lymphoid malignancies. Recent studies suggested the important role of dysregulation of the endogenous immune system in lymphomagenesis. The relationships between cytokines/chemokines and their receptors, are important in determining the selectivity of local immunity. To investigate differences in the endogenous immune system of diffuse large B cell lymphoma (DLBL), we performed gene expression profiling using cDNA microarrays of cytokines/chemokines and their receptors. We studied 5 cases each of primary central nervous system lymphomas (PCNSL), extranodal and nodal lymphomas. PCNSL exhibited diffuse down-regulated profiles, compared to normal peripheral blood lymphocytes. While extranodal and nodal lymphomas also exhibited diffuse down-regulated profiles, some genes displayed up-regulated profiles. Hierarchical clustering analysis separated PCNSL and extranodal lymphomas into distinct groups based on their gene expression profiles, as well as extranodal and nodal, but not PCNSL and nodal. PCNSL exhibited significantly lower expression of BLC/BCA-1 and CCR-3 (Th2 type), and higher expression of IL-8 and MIP-1beta (Th1 type) than extranodal lymphomas. Immunohistochemistry and RT-PCR revealed frequent CCR-3 and BLC/BCA-1 expression in extranodal lymphomas, compared with PCNSL. Our results provide new insights into the pathogenesis of each DLBL. A better understanding of the immune response in each DLBL could help in the design of novel therapeutic strategies based on cytokines/chemokines and their receptors.
 ...
PMID:Differential expression of chemokines, chemokine receptors, cytokines and cytokine receptors in diffuse large B cell malignant lymphoma. 1476 37

Mycoplasma hyopneumoniae (Mh) is the primary agent of porcine enzootic pneumonia (PEN), a chronic respiratory disease endemic to pig farms, and characterized histologically by infiltration of mononuclear cells in airways and prominent hyperplasia of the bronchus-associated lymphoid tissue (BALT). To gain further insight into the pathogenesis of PEN, cytokine expression in the lung, with particular attention to the BALT, was examined immunohistochemically in pigs naturally infected with Mh. An increase (P < 0.05) in proinflammatory and immunoregulatory cytokines (especially interleukin [IL]-2, IL-4 and tumour necrosis factor [TNF]-alpha, and to a lesser extent IL-1 [alpha and beta] and IL-6) was detected in the BALT, which showed intense lymphoid hyperplasia. IL-1beta and TNF-alpha were also detected in the bronchoalveolar exudate of infected pigs, and IL-6 and IL-8 were demonstrated in mononuclear cells of the alveolar septa. The results showed that in Mh infection, macrophage and lymphocyte activation results in the expression of a number of cytokines capable of inducing lung lesions and lymphoreticular hyperplasia of the BALT.
 ...
PMID:Immunohistochemical labelling of cytokines in lung lesions of pigs naturally infected with Mycoplasma hyopneumoniae. 1505 34


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>