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)

Tepoxalin, a dual enzyme inhibitor of cyclooxygenase and 5-lipoxygenase has been shown to inhibit T-cell activation. Its immunosuppressive property is distinct from cyclosporin because only tepoxalin, but not cyclosporin, suppresses NF-kappa B activation. Here we report that tepoxalin selectively inhibits intercellular adhesion molecule-1 (ICAM-1, CD54)/MAC-1 (CD11b/CD18) dependent adhesion of polymorphonuclear cells to IL-1 activated human umbilical vein endothelial cells. The mechanism of inhibition is related to the surface expression of several cell adhesion molecules. Flow cytometry analyses on cultured cells that were treated with tepoxalin or antisense oligonucleotides to the P65/p50 subunit of NF-kappa B, and then stimulated with PMA, revealed a reduced expression of CD11b/CD18 on monocytic HL60 cells, and endothelial adhesion molecule-1 (CD62E) and vascular adhesion molecule-1 (CD106) on human umbilical vein endothelial cells. Expression of other adhesion molecules such as lymphocyte function associated-antigen-1 (CD11a/CD18) and CD54 were unaffected. Tepoxalin also inhibited the secretion of a NF-kappa B regulated chemokine, IL-8, a known inducer of CD11b/CD18 expression. Thus the suppression of CD11b/CD18 expression by tepoxalin may involve IL-8. Our results suggest that by inhibiting NF-kappa B activation, surface expression of several adhesion molecules can be modulated and that tepoxalin may be useful in treating selected adhesion mediated events such as leukocyte migration or atherosclerotic plaque formation.
 ...
PMID:The NF-kappa B inhibitor, tepoxalin, suppresses surface expression of the cell adhesion molecules CD62E, CD11b/CD18 and CD106. 902 87

The microvascular endothelial cell (MVEC) is a major target of inflammatory cytokines overproduced in conditions such as sepsis and infectious diseases. We addressed the direct and indirect effects of tumor necrosis factor (TNF) on endothelial cells that can be relevant for the pathogenesis of septic shock, with particular attention to the acute respiratory distress syndrome (ARDS) and to cerebral malaria (CM). To identify functional and phenotypical changes occurring in MVEC during sepsis, we isolated these cells from the lungs of patients who died of ARDS. The constitutive expression of ICAM-1 and, to a lesser extent, VCAM-1, CD14, and TNFR2 were significantly increased on MVEC isolated from ARDS patients compared with control MVEC, whereas ELAM-1 and TNFR1 were not increased. We found that lung MVEC from ARDS patients present a procoagulant profile and a higher production capacity of interleukin-6 (IL-6) and IL-8 when compared with those from controls. As in pulmonary MVEC derived from ARDS patients, the only TNFR type found up-regulated in brain microvessels during CM was TNFR2. This increase in TNFR2 expression only occurred in CM-susceptible mice at the onset of the neurological syndrome. We therefore investigated the role of TNFR2 in the development of this brain pathology by comparing the incidence of CM in wild-type and TNF receptor knock-out mice. Unexpectedly, the genetic deficiency in TNFR2, but not in TNFR1, conferred protection against CM and its associated mortality. No ICAM-1 up-regulation was detected in the brain of Tnfr2 knockout mice, indicating a close correlation between protection against CM-associated brain damage, absence of TNFR2, and absence of ICAM-1 up-regulation in the brain. Our results in ARDS and CM indicate a specific up-regulation of TNFR2, but not of TNFR1, on lung and brain MVEC, respectively. This increased expression leads to a reduced sensitivity toward TNFR1-mediated phenomena, such as the sensitized TNF cytolytic activity on lung MVEC. In contrast, the sensitivity toward TNFR2-mediated effects, such as ICAM-1 induction by membrane-bound TNF, is increased on brain and lung MVEC expressing increased levels of TNFR2. Therefore, the ICAM-1-inducing effect, rather than the direct cytotoxicity of inflammatory cytokines, such as TNF, appears to be crucial in ARDS and CM-induced endothelial damage, and TNFR2 seems to play an important role in this activity in vivo.
 ...
PMID:TNF receptors in the microvascular pathology of acute respiratory distress syndrome and cerebral malaria. 912 3

Psoriatic arthritis (PA) is an inflammatory rheumatic disease that can concomitantly occur in patients with psoriasis vulgaris. Psoriatic synovitis shows alterations of the synovial microvasculature. Inflammatory cells adhere to endothelial cells (EC) and migrate through the vascular wall of postcapillary venules located in the subintimal layer of the synovial membrane. The aim of our study was to investigate, first, the phenotype of lymphocytes (LC) of PA patients using flow cytometry (FC) with regard to activation antigens and adhesion molecules; second, the adhesion of LC of PA patients on cultivated resting or activated (with thrombin, LPS, IFN-gamma, or TNF-alpha) human umbilical vein endothelial cells (HUVEC) by counting the Feulgen-stained nuclei of both adherent LC and HUVEC using image analysis; and third, the synthesis of IL-6 and IL-8 in both LC and HUVEC 24 hr after cell contact. These cytokines were determined qualitatively by immunofluorescence and quantitatively at the single-cell level by FC as well as in the supernatants of the cultures using commercial cytokine ELISAs. Fourth, we investigated whether or not the LC adhesion on HUVEC as well as the cytokine production could be inhibited by monoclonal antibodies against LC- or EC-specific adhesion molecules. In contrast to controls PA patients showed an increased surface expression of CD11a, b, and c as well as of CD44 but a reduced surface expression of CD49d/CD29, and CD49e/CD29, and cell-bound fibronectin on CD3+ LC. The activation markers CD25 and HLA-DR were found to be slightly enhanced in PA. The cell adhesion was generally enhanced in PA patients vs controls. It could be reduced with monoclonal antibodies (MoAbs) against CD11a and CD18 on IFN-gamma- or TNF-alpha-activated HUVEC but was generally enhanced after treatment of HUVEC with MoAbs against CD54, CD62E, or CD106. Due to LC adhesion on HUVEC IL-6 and IL-8 were produced in significantly higher amounts in PA patients compared to controls. This effect occurred already in resting but was enhanced in activated HUVEC. While IL-6 is mainly produced by HUVEC but also in smaller quantities by LC, IL-8 is synthesized only by HUVEC and could be modified by preincubation with MoAbs against LC- or EC-specific adhesion molecules in parallel to the cell adhesion. The experiments show that the main adhesion pathway in LC homing of PA patients is the interaction of the LC adhesion molecule CD11a/CD18 with CD54 on EC followed by an enhanced synthesis of proinflammatory and chemotactic cytokines. These results favor the hypothesis that the pathological alterations of the microvasculature in PA patients are generated by altered homing processes.
 ...
PMID:Interactions of lymphocytes from patients with psoriatic arthritis or healthy controls and cultured endothelial cells. 940 Jun 30

Serum cytokine levels were measured in 275 healthy children of different ages (3 to 17 years). Interleukin-1 receptor antagonist (IL-1RA), soluble IL-2R (sIL-2R) (sCD25), IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), soluble TNF receptor type II (sTNF-RII) (sCD120b), gamma interferon (IFN-gamma), soluble intercellular adhesion molecule 1 (sICAM-1) (sCD54), soluble E selectin (sE-selectin) (ELAM-1; sCD62E), sCD14, and neopterin were measured with commercial test kits. The mean levels of IL-1RA, sIL-2R, TNF-alpha, sICAM-1, sE-selectin, and sCD14 were higher than in healthy adults. In contrast, IFN-gamma and IL-8 were hardly detectable in children and thereby significantly lower than in adults. In the case of TNF-alpha, sICAM-1, sE selectin, and sCD14, there was a high interindividual variability, apparently unrelated to disease. The profiles of some cytokines, i.e., IL-1RA, IL-6, and TNF-alpha, showed age-related increases that overlapped with known patterns of physical growth. Of note, sIL-2R and sE-selectin instead declined with time. Because of the remarkable age-dependent variability in healthy pediatric subjects, disease-related changes, as well as therapy-dependent alterations, should be considered with caution.
 ...
PMID:Age-dependent levels of select immunological mediators in sera of healthy children. 945 75

Cervical ripening at term resembles an inflammatory reaction with invasion of activated granulocytes into the cervical stroma. Our objective was to investigate the influence of the antigestagen onapristone alone and in combination with other substances associated with cervical ripening on the expression of the inflammation-associated adhesion molecules ELAM-1, ICAM-1 and VCAM-1. Human endothelial cell cultures were stimulated with onapristone (200 ng/ml), TNF-alpha (100 U/ml), IL-8 (20 ng/ml) and PGE2 (3 ng/ml) separately and in combination (n = 6). The expression of adhesion molecules was determined qualitatively and quantitatively by immunofluorescence staining and flow cytometry with statistical evaluation by Kolmogorov-Smirnov analysis. Onapristone upregulated slightly the expression of ELAM-1 (19%). The costimulation of onapristone and TNF-alpha provoked an additive expression of VCAM-1 (64%) beyond the effect of TNF-alpha alone, while the costimulation of onapristone and PGE2 as well as the combination with IL-8 did not result in an additional stimulatory effect. All results were statistically significant (p < 0.001). This result supports our hypothesis that onapristone may lead to an increased adhesion of granulocytes to the capillary endothelium thereby initiating cervical ripening.
 ...
PMID:Cervical dilatation: induction by antigestagens via adhesion molecules. An in vitro examination in endothelial cell cultures. 951 4

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.
 ...
PMID:Nonspecific and immune-specific up-regulation of cytokines in rabbit dermal tuberculous (BCG) lesions. 954 73

Previous reports have highlighted the disparity in biocompatibility of two differently engineered heparin coatings during the cardiopulmonary bypass (CPB) procedure. The aim of this prospective study was to evaluate the impact of the difference in haemocompatibility provided by either the Duraflo II equipment or the Carmeda equipment in the terminal inflammatory response observed after coronary artery surgery. Thirty patients were randomly allocated to two groups to be operated on using either Duraflo II equipment (group I) or Carmeda equipment (group 2) for extracorporeal circulation (ECC). Initial inflammatory response was assessed by terminal complement complex activation (SC5b-9). The late inflammatory response observed in the postoperative period was assessed by measuring cytokine production (tumour factor necrosis (TNF alpha), interleukin IL-6, interleukin IL-8) and circulating concentrations of adhesion molecules (ELAM-1, ICAM-1). The release of SC5b-9 after CPB and after protamine administration was lower in group 2 than in group 1 (p = 0.0002 and p = 0.006, respectively). A significant production of cytokines was detected in both groups with peak values observed within the time range of 4-6 h after the start of CPB.
 ...
PMID:Inflammatory response to cardiopulmonary bypass using two different types of heparin-coated extracorporeal circuits. 988 89

The present study focusses on the effects of ibuprofen and its enantiomers on cytokine production by peripheral blood monocytes and endothelial cells as well as on the potential modulation of ADM-expression by human umbilical vein endothelial cells and the concomitant effects on monocyte transendothelial migration as measured by a cell migration assay system. This consists of an endothelial cell monolayer on a solid collagen substrate, i.e. an artificial vessel wall construct. We observed a significant inhibition by 100 microg/ml ibuprofen of VCAM-1 expression by endothelial cells while ELAM-1 and ICAM-1 expression was not influenced. However, we could not see any concomitant inhibitory effects on the spontaneous migration of monocytes after preincubating the endothelial cell monolayer with ibuprofen up to concentrations of 100 microg/ml and activating with suboptimal and optimal concentrations of TNF-alpha. Our monocyte transendothelial migration system reflects very sensitively endothelial cell-activation even by very low TNF-alpha concentrations. (S)- and (R)-ibuprofen were equal in their inhibitory/activating effects on cytokine production, with the exception of stronger IL-8 induction in endothelial cells by (R)-ibuprofen as compared to its chiral analogue.
 ...
PMID:Inhibition of cytokine production and adhesion molecule expression by ibuprofen is without effect on transendothelial migration of monocytes. 1039 61

Cytokine mediators and leukocyte-endothelial cell adhesion molecules are critical and interdependent components of the acute inflammatory response in sepsis. We hypothesized that the administration of monoclonal antibodies to intercellular adhesion molecule-1 (CD54) or E- and L-selectin (CD62E/L) would decrease serum levels of the proinflammatory cytokines interleukin-1beta (IL-1), IL-6, and IL-8 and tumor necrosis factor receptor (TNFR-1) in baboons during sepsis. Adult male baboons received infusions of 1 x 10(9) colony forming units (CFU)/kg heat-killed Escherichia coli (E. coli) followed 12 h later by live E. coli (1 x 10(10) CFU/kg). At the time of live bacterial infusion, six septic animals were treated with a monoclonal antibody to CD54 and six with an antibody to CD62E and L (1 mg/kg). Eight untreated septic animals served as controls. Sequentially drawn serum samples were assayed for IL-1, IL-6, IL-8, and TNFR-1 using enzyme-linked immunoassay (ELISA). Data were compared using Mann-Whitney U tests and Chi-square analyses. Median survival was decreased in both treatment groups compared to controls (P < 0.05). Peak IL-1 level was higher than controls in septic animals treated with anti-CD54 but not anti-CD62E/L (P < 0.05, P = NS, respectively). Elevations in IL-6, IL-8, and TNFR-1 were increased and prolonged in both antibody treated groups compared to controls (P < 0.05). These results provide the first in vivo evidence that leukocyte-endothelial adhesion molecules CD54 and CD62E/L regulate cytokine production in sepsis.
 ...
PMID:Proinflammatory cytokines increase in sepsis after anti-adhesion molecule therapy. 1080 17

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.
 ...
PMID:Hantavirus infection induces the expression of RANTES and IP-10 without causing increased permeability in human lung microvascular endothelial cells. 1139 Jun 9


<< Previous 1 2 3 Next >>