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 evaluation of the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) would appear to be important in cancer patients. Since the activity of these enzymes is regulated at the gene level by cytokines, we studied the serum relationships between MMP1/TIMP1 and the network of TH1/TH2 cytokines in healthy subjects to better understand how the physiological network of cytokines regulates MMP1/TIMP1 activity. Such a study could lead to suggestions for follow-up experiments to create prognostic and diagnostic indices for more efficient disease prevention programs and biotherapeutic treatments of patients. For this purpose, we determined serum levels of MMP1, TIMP1 and interleukin (IL)2, interferon (IFN) gamma, IL4 and IL10 in both healthy men and women (men and women were analyzed separately as hormones are one of the non-cytokine regulatory factors of TH1 or TH2 polarization). These cytokines make up our basic network. Cytokines within the physiological network function simultaneously so mathematical models of multivariate statistical methods were used to study MMP1/TIMP1 and TH1/TH2 network relationships. It has been suggested that mathematical modeling is the only effective way of studying the immune system as a whole. The influence of network activation, antigen presenting cells, antibody response and chemokines on MMP1/TIMP1 balance was also studied. Network activation was evaluated by measuring the levels of soluble IL2 receptors (sIL2R) and sIL6R; the influence of antigen presenting cells was evaluated by measuring serum levels of tumor necrosis factor alpha (TNF alpha) and IL1 beta; antibody response was evaluated by measuring IL5 and IL6 serum levels and the influence of chemokines was evaluated by measuring serum levels of IL8. Our overall results suggest that there are relationships between the activity of MMP1/TIMP1 and the TH1/TH2 network in physiological conditions. These data may be useful in gaining a clearer insight into how the two systems interact and hence regulate the physiological homeostasis. Therefore, this paper provides suggestions for experimental studies on MMP1/TIMp1 enzymes and TH1/TH2 cytokines to create clinical and prognostic markers for patient evaluation.
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PMID:Relationships between the activity of MMP1/TIMP1 enzymes and the TH1/TH2 cytokine network. 1085 Mar 33

Our previous data on colorectal cancer suggest that there are faults at the level of mechanisms of the proliferative responses of patients peripheral blood mononuclear cells (PBMC) to the interleukin (IL)-2 and IL-2 PBMC production, which increase with the stage advancement. The damages in the proliferative response seem to be eliminated by the costimulator effects of the signals produced by the anti-CD3 monoclonal antibody (antiCD3), and the disregulation in TH subsets of CD4+ T cells with a malfunction of TH1 cells and an expansion of TH2, might contribute to this situation. So, by using biotherapeutic treatments to allow the generation of productive immune response in these patients it is essential to identify the defect in their immune system to discover how these mechanisms should be appropriately manipulated in vivo to switch their immune response from a non-productive to a productive one. We have studied this in a group of patients and healthy subjects as the control group, performing their immunological evaluation by determining these parameters: serum levels of IL-2, interferon (IFN) gamma, IL-4, IL-6, IL-7, IL-8, tumour necrosis factor (TNF) alpha, soluble IL-2 receptor (sIL-2R), intercellular adhesion molecule 1 (sICAM-1) and CD30 (sCD30) molecules; PBMC phenotypic antigens expression (CD3, CD4, CD8, CD19, CD16, CD56, CD57, CD25) on peripheral blood mononuclear cells (PBMC); proliferative response of PBMC to IL-2, IL-4 and anti-CD3 monoclonal antibody (antiCD3). Moreover, since mutant c-Ki-ras oncogene is a very frequent finding in colorectal cancers and there are indications which suggest its involvement in tumour progression, the analysis of c-ki-ras codon 12 and 13 were determined and the statistical evaluation of the above immunological parameters were performed by comparing the patient groups with (M+) and without (M-) these mutations with each other, and with the healthy group. The results underline the necessity of biotherapeutic treatments inducing TH1 cell functions in these patients. Moreover in M+ it seems also important to solve the problem of the switch from B to macrophage cells as immune cells which present antigens, and the possible involvement of c-Ki-ras gene mutations in the impairment of T cell receptor activation (TCR).
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PMID:Necessity of biotherapeutic treatments inducing TH1 cell functions in colorectal cancer. 1085 98

Cytokine regulation of lymphocyte survival may play an important role in the control of the cell cycle during the immune response both in health and disease. Expression of the Bcl2 gene promotes cell survival by countering apoptosis stimuli. The p53 protein has been implicated in the control of the cell cycle, in the synthesis and repair of DNA and in programmed cell death. TH1 and TH2 cytokines exert a mutual cross-regulation on the precursors of TH1- or TH2-type effector cells which are important mediators in directing the immune system towards the appropriate response. TH1 and TH2 cytokines have also been implicated in the modulation of the expression of cell cycle regulator genes. Therefore, the study of the relationships between TH1 and TH2 cytokines and Bcl2 and p53 molecules in healthy subjects could lead to a better understanding of the physiological regulation of the immune response and identify markers for prognostic and diagnostic indices and biotherapeutic treatment. We determined the serum levels of cytokines (IL2, IFN gamma, IL4, IL10, IL5, IL6, IL1 beta, TNF alpha, IL8), soluble receptors (sIL2R, sIL6R), Bcl2-protein and p53-antibody in a group of healthy subjects. Multivariate statistical analyses were used to study the cytokine network relationships with Bcl2-protein and p53-antibody, as they allow a simultaneous evaluation of all variables which reflects the physiological situation. Our overall results suggest that relationships exist between TH1 and TH2 cytokines and the Bcl2-protein and p53-antibody in physiological conditions. This information could now be used in experimental studies to create diagnostic and prognostic indices for the monitoring of health and disease.
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PMID:Cell cycle control in cellular homeostasis during the immune response: interactions between TH1, TH2 cytokines, and Bcl2 and p53 molecules. 1127 99

Sin Nombre virus (SNV) and Hantaan virus (HTN) infect endothelial cells and are associated with different patterns of increased vascular permeability during human disease. It is thought that such patterns of increased vascular permeability are a consequence of endothelial activation and subsequent dysfunction mediated by differential immune responses to hantavirus infection. In this study, the ability of hantavirus to directly induce activation of human lung microvascular endothelial cells (HMVEC-Ls) was examined. No virus-specific modulation in the constitutive or cytokine-induced expression of cellular adhesion molecules (CD40, CD54, CD61, CD62E, CD62P, CD106, and major histocompatibility complex classes I and II) or in cytokines and chemokines (eotaxin, tumor necrosis factor alpha, interleukin 1beta [IL-1beta], IL-6, IL-8, MCP-1, MIP-1alpha, and MIP-1beta) was detected at either the protein or message level in hantavirus-infected HMVEC-Ls. Furthermore, no virus-specific enhancement of paracellular or transcellular permeability or changes in the organization and distribution of endothelial intercellular junctional proteins was observed. However, infection with either HTN or SNV resulted in detectable levels of the chemokines RANTES and IP-10 (the 10-kDa interferon-inducible protein) in HMVEC-Ls within 72 h and was associated with nuclear translocation of interferon regulatory factor 3 (IRF-3) and IRF-7. Gamma interferon (IFN-gamma)-induced expression of RANTES and IP-10 could also be detected in uninfected HMVEC-Ls and was associated with nuclear translocation of IRF-1 and IRF-3. Treatment of hantavirus-infected HMVEC-Ls with IFN-gamma for 24 h resulted in a synergistic enhancement in the expression of both RANTES and IP-10 and was associated with nuclear translocation of IRF-1, IRF-3, IRF-7, and NF-kappaB p65. These results reveal a possible mechanism by which hantavirus infection and a TH1 immune response can cooperate to synergistically enhance chemokine expression by HMVEC-Ls and trigger immune-mediated increases in vascular permeability.
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PMID:Hantavirus infection induces the expression of RANTES and IP-10 without causing increased permeability in human lung microvascular endothelial cells. 1139 Jun 9

The benefit of neutrophil exclusion from type 1 T helper cell (TH1) inflammatory processes was demonstrated in clinical studies. Increased recruitment of lymphocytes and monocytes to endothelium and impaired recruitment of polymorphonuclear neutrophils (PMNs) following interferon-gamma (IFN-gamma) treatment were described. The present study demonstrates that a 24 h treatment with IFN-gamma increases interleukin (IL)-6 release but reduces IL-8 secretion of both untreated and of tumor necrosis factor-alpha (TNF-alpha)-stimulated endothelial cells (ECs), favoring the attraction of lymphocytes but not of neutrophils. Alteration of cytokine release was accompanied by reduced basal and TNF-alpha-stimulated nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1) activity. However, IFN-gamma application neither altered gene expression of both TNF-alpha receptors (p55 and p75) nor cellular density of TNF-alpha receptor-2 (p75). Therefore, immune-modulatory action of IFN-gamma seems to be mediated by signal transduction molecules.
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PMID:Contrasting effects of long-term treatment with IFN-gamma in endothelial cells: increase in IL-6 secretion versus decrease in IL-8 secretion, NF-kappa B, and AP-1 activation. 1238 Jun 42

The adherence to and invasion of the human epithelial cell line A549 by group B streptococcus (GBS) serotype VIII strains were compared with those of serotype III strains by a conventional method and the dynamic in vitro attachment and invasion system. Twenty GBS strains, including nine vaginal isolates and one invasive isolate each of serotypes III and VIII, were used in the conventional attachment and invasion assay. Adherence to and invasion of A549 cells by serotype VIII GBS strains were significantly greater (P < 0.0001) than those by serotype III strains for both the invasive strain and vaginal isolates. Cytokine production by A549 cells following stimulation with GBS serotypes III and VIII or their purified capsular polysaccharides (CPS) was measured. Serotype III strains stimulated significantly greater tumor necrosis factor alpha (TNF-alpha) (P < 0.0001) and interleukin-10 (IL-10) (P < 0.05) production than did serotype VIII strains. IL-8 production in response to serotype VIII was significantly higher (P < 0.001) than that in response to serotype III. TNF-alpha, IL-8, and IL-10 production was greater in A549 cells infected with GBS than in the untreated control cells. TNF-alpha production was significantly greater (P < 0.005) after stimulation with purified GBS serotype III CPS than after stimulation with serotype VIII CPS, a result similar to that after stimulation with whole GBS. IL-12 production by A549 cells was observed only in response to infection with GBS serotype III, resulting in the possibility of a greater TH1 response in serotype III GBS. These results suggest differences in immune responses to infection with GBS serotypes III and VIII.
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PMID:Adherence to, invasion by, and cytokine production in response to serotype VIII group B Streptococci. 1527 33

Hepatitis C virus (HCV) is remarkably efficient at establishing persistent infection, suggesting that it has evolved one or more strategies aimed at evading the host immune response. T cell responses, including interferon-gamma production, are severely suppressed in chronic HCV patients. The HCV core protein has been previously shown to circulate in the bloodstream of HCV-infected patients and inhibit host immunity through an interaction with gC1qR. To determine the role of the HCV core-gC1qR interaction in modulation of inflammatory cytokine production, we examined interleukin (IL)-12 production, which is critical for the induction of interferon-gamma synthesis, in lipopolysaccharide-stimulated human monocyte/macrophages. We found that core protein binds the gC1qR displayed on the cell surface of monocyte/macrophages and inhibits the production of IL-12p70 upon lipopolysaccharide stimulation. This inhibition was found to be selective in that HCV core failed to affect the production of IL-6, IL-8, IL-1beta, and tumor necrosis factor alpha. In addition, suppression of IL-12 production by core protein occurred at the transcriptional level by inhibition of IL-12p40 mRNA synthesis. Importantly, core-induced inhibition of IL-12p40 mRNA synthesis resulted from impaired activation of AP-1 rather than enhanced IL-10 production. These results suggest that the HCV core-gC1qR interaction may play a pivotal role in establishing persistent infection by dampening TH1 responses.
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PMID:Hepatitis C virus core selectively suppresses interleukin-12 synthesis in human macrophages by interfering with AP-1 activation. 1529 84

Prophylactic vaccinations may sometimes shorten the incubation period of some illnesses and/or convert a latent infection/inflammation into a clinically apparent disease. Cytokines play a major role in mediating the inflammatory process in various clinical entities and represent a potential source of tissue damage if their production is not sufficiently well controlled. It seems that irregularities in production of proinflammatory cytokines may be responsible for the abnormalities associated with full-blown clinical symptoms of various urinary tract diseases observed after DTP vaccination in 13 infants and young children hospitalized over the past 24 years. On admission, upper respiratory tract diseases, atopic dermatitis, and/or latent urinary tract infection/inflammation were found in these children. It is suggested that the whole-cell pertussis present in DTP vaccine, acting as an excessive stimulus in these patients, produced symptoms reminiscent of biologic responses to circulating proinflammatory monokines such as IL-1beta, TNF-alpha, and IL-6 because earlier it was reported that in vitro the whole-cell vaccine induced significantly more such cytokine production than did the acellular pertussis or diphtheria-tetanus-only vaccine. Analysis of the cellular immune disturbances previously reported in urinary tract infection/inflammation (increased serum and/or urinary IL-1alpha, IL-1 receptor antagonist, IL-6 and IL-8), steroid-sensitive nephrotic syndrome (increased IL-2, IFN-gamma, TNF-alpha, and decreased or increased IL-4, depending on the cells studied), and atopic dermatitis (decreased IFN-gamma and increased IL-4 production), may suggest that similar subclinical chronic cytokine-mediated abnormalities produced in the course of latent diseases revealed in our patients, combined with those caused by DTP vaccination stimulus, were responsible for the pathomechanism of these clinical entities. This speculation is in agreement with the reports on the long-lasting induction of cytokine release and down-regulation of hepatic cytochrome P-450 isoenzyme activities after administration of DTP vaccine to mice and may be supported by the fact that TH1 phenotype is associated with the up-regulation of intercellular adhesion molecule-1 and RANTES, whereas TH2 phenotype is associated with the up-regulation of the vascular cell adhesion molecule and P-selectin, which are key players in the migration into inflamed tissues and localization of lymphocytes and other allergic effector and inflammatory cells. Because several inflammatory cytokines down-regulate gene expression of major cytochrome P-450 and/or other enzymes with the specific effects on mRNA levels, protein expression, and enzyme activity, thus affecting the metabolism of several endogenous lipophilic substances such as steroids, lipid-soluble vitamins, prostaglandins, leukotrienes, thromboxanes, and exogenous substances, their irregularities in the body may eventually lead to the flare of latent diseases in some predisposed subjects. Also, interleukin genetic polymorphisms, especially the constellation of TNF-alpha and IL-6 genetic variants, might predispose some infants with infection to a more than usually intense inflammatory response in the kidneys after vaccination. It seems that the aforementioned pathomechanism may also be responsible for some cases of sudden infant death syndrome, which is often preceded by infection/inflammation.
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PMID:Urinary tract diseases revealed after DTP vaccination in infants and young children: cytokine irregularities and down-regulation of cytochrome P-450 enzymes induced by the vaccine may uncover latent diseases in genetically predisposed subjects. 1535 30

Neisseria gonorrhoeae is an obligate human pathogen that represents a significant health concern, particularly in the developing world. Although generally associated with an acute inflammatory infection of urogenital epithelia cells, infections have been noted in multiple tissues and many infected individuals can become asymptomatic carriers. Few studies of immune response to N. gonorrhoeae infection in peripheral blood have evaluated the production of T helper cytokines (TH1/TH2) induced early after infection. We developed a quantitative realtime PCR assay based on the gonococcal rmpIII gene to monitor dose-response effects of infection on cytokine release from peripheral blood mononuclear cells (PBMCs). We observed upregulation of CD69 transcription and surface CD25 expression on lymphocytes, consistent with early T-cell activation. We observed dosage-dependent transcription of the chemotactic factor IL-8 and previously unreported activation of the chemoattractant MCP-2. Multiplex analysis of broad cytokine protein production revealed a differential increase in the TH1 and TH2 associated cytokines: IL-2, IL-4, IL-8, IL-10, IL-12, IFN-gamma, TNF-alpha and MCP-1. Markov models of protein accumulation implicated a cross-regulated response to infection, notably for IL-8, IL-10 and IL-12. Taken together, the cytokine profile we observed early in response to whole gonococcal bacteria was broader than has been previously described and may have relevance for the contribution of antagonistic signaling events early in infection and in understanding peripheral immune mechanisms engaged to control infection.
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PMID:Evidence for cross-regulated cytokine response in human peripheral blood mononuclear cells exposed to whole gonococcal bacteria in vitro. 1662 26

Increased blood-brain-barrier (BBB) permeability precedes any clinical or pathologic signs and is critical in the pathogenesis of multiple sclerosis (MS) and brain metastases. CD4+ TH1 cells mediate demyelination in MS, but how they get sensitized and enter the brain to induce brain inflammation remains obscure. TH2 cytokines associated with allergic disorders have recently been implicated in MS, while genes upregulated in MS plaques include the mast cell-specific tryptase, the IgE receptor (Fc-epsilon-RI) and the histamine-1 receptor. Mast cell specific tryptase is elevated in the CSF of MS patients, induces microvascular leakage and stimulates protease-activated receptors (PAR), leading to widespread inflammation. BBB permeability, MS and brain metastases appear to worsen in response to acute stress that leads to the local release of corticotropin-releasing hormone (CRH), which activates brain mast cells to selectively release IL-6, IL-8 and vascular endothelial growth factor (VEGF). Acute stress increases BBB permeability that is dependent on CRH and mast cells. Acute stress shortens the time of onset of experimental alleric encephalomyelitis (EAE) that does not develop in W/W mast cell deficient or CRH -/- mice. Brain mast cell inhibition and CRHR antagonists offer novel therapeutic possibilities.
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PMID:Corticotropin-releasing hormone and the blood-brain-barrier. 1712 8


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