Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The allergen-induced late nasal response (LNR) is associated with high expression of interleukin-4 (IL-4) and IL-5 messenger RNA (mRNA) in the nasal mucosa, suggesting a role for Th2-type cytokines in the development of the LNR. Moreover, topical corticosteroid-mediated inhibition of the LNR is accompanied by inhibition of IL-4, but not IL-5, mRNA expression, IL-13 shares a number of functions with IL-4, including IgE switching and vascular cell adhesion molecule-1 (VCAM-1) upregulation. We investigated the expression of IL-13 mRNA and immunoreactivity in nasal biopsies from 10 normal subjects and 20 subjects with allergic rhinitis. IL-4 mRNA expression was examined in the same subjects. The allergic rhinitis patients were randomized to receive a 6-wk treatment with either topical fluticasone propionate (n = 10) or placebo (n = 10) nasal spray twice daily. A nasal biopsy was taken before treatment and 24 h after local nasal allergen provocation with a grass-pollen extract. Before treatment, there was no significant difference between the allergic rhinitis patients and controls in the expression of IL-13 mRNA and immunoreactivity. After allergen provocation, we observed a significant increase in IL-13 mRNA-positive and immunoreactive cells at 24 h only in subjects given placebo (P < 0.001). Inhibition of the LNR after corticosteroid treatment was associated with a marked decrease in allergen-induced IL-13 mRNA-positive (P < 0.001) and immunoreactive cells (P < 0.001). In subjects given placebo, 76.9 +/- 5.5% of IL-13 mRNA-positive cells observed after allergen were CD3+, whereas 11.2 +/- 2.7% coexpressed immunoreactivity for mast-cell tryptase. In these subjects, increases in cells expressing IL-13 mRNA were greater than for IL-4 mRNA (P = 0.001), and double in situ hybridization studies revealed that 100% of the IL-4 mRNA-positive cells coexpressed IL-13 mRNA, whereas 66.6 +/- 10.5% of IL-13 mRNA-positive cells coexpressed IL-4 transcripts after allergen challenge. The results of this study suggest that IL-13 expression is a prominent feature of the LNR, and that inhibition of the LNR following steroid therapy may be partly attributable to inhibition of IL-13 expression.
Am J Respir Cell Mol Biol 1997 Jul
PMID:IL-13 mRNA and immunoreactivity in allergen-induced rhinitis: comparison with IL-4 expression and modulation by topical glucocorticoid therapy. 922 5

Airway epithelium may actively participate in inflammatory responses, such as occur in asthma. The presence and regulation of surface molecules on the airway epithelium, however, is incompletely understood. We have determined the phenotype of the human bronchial epithelial cell line BEAS-2B by flow cytometry. We confirmed previous observations that human bronchial epithelial cells constitutively express CD29, CD44, CD49a, CD49b, CD49c, CD49d, CD49e, CD49f, CD51, CD54 (ICAM-1), CD61, and HLA class 1. BEAS-2B cells were also found to constitutively express CD9, CD13, CD15, CD15s, CD23, CD33, CD36, CD40, CD41b, CD42b, CD48, CD50, CD71, and CD102 (ICAM-2). Culture of BEAS-2B cells with tumor necrosis factor (TNF)-alpha or interleukin (IL)-1beta (1 ng/ml) was found to enhance intercellular adhesion molecule-1 (ICAM-1) expression (several fold) and induce de novo CD106 [vascular cell adhesion molecule-1 (VCAM-1)] expression. TNF-alpha or IL-1beta did not change the expression of CD9, CD13, CD16, CD23, CD29, CD31, CD32, CD35, CD45, CD61, or CD64 in BEAS-2B cells. IL-4 (1 ng/ml) also induced expression of VCAM-1 (1.5-fold) but not ICAM- expression while interferon-gamma (1 ng/ml) enhanced only ICAM-1 expression (2-fold). Maximal VCAM-1 expression was obtained with the combination of TNF-alpha and IL-4 (8-fold). Using Northern blot hybridization analysis, ICAM-1 and VCAM-1 mRNA was detected in BEAS-2B cells stimulated with cytokines. VCAM-1 on stimulated BEAS-2B was functionally active as determined by adhesion of purified eosinophils and blockade with specific antibodies. Primary isolates of bronchial epithelial cells produced detectable levels of VCAM-1 protein and mRNA as detected by enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction, respectively. These results suggest that cytokine activation induces expression of ICAM-1 and VCAM-1 on airway epithelium, an event which may influence leukocyte infiltration and activation.
Am J Respir Cell Mol Biol 1997 Nov
PMID:Phenotyping and cytokine regulation of the BEAS-2B human bronchial epithelial cell: demonstration of inducible expression of the adhesion molecules VCAM-1 and ICAM-1. 937 8

We investigated whether interleukin-1alpha (IL-1) would induce gene expression of vascular cell adhesion molecule-1 (VCAM-1) in cardiac myocytes and, if so, whether nuclear factor kappaB (NF-kappaB) was involved. We evaluated the VCAM-1 gene expression in cultured neonatal rat cardiac myocytes by the reverse transcription-polymerase chain reaction. IL-1 alone or together with interferon-gamma (IFN) induced VCAM-1 gene expression in the cells. Induction of VCAM-1 gene expression in response to IL-1 and IFN was antagonized in a concentration-dependent manner by pyrrolidine dithiocarbamate, an inhibitor of NF-kappa b activation (25-100 microM). Tosyl-lysine-chloromethyl ketone, another inhibitor of NF-kappa b activation, also inhibited the expression of the VCAM-1 gene in response to IL-1 and IFN. Thus, VCAM-1 gene expression appeared to be mediated by NF-kappa b in cardiac myocytes, and this cardiac myocyte VCAM-1 may be involved in cardiac inflammatory disorders. Disruption of expression of VCAM-1 by inhibition of NF-kappa b activation may indicate a target for pharmacologic intervention intended to limit cardiac inflammation.
Mol Cell Biochem 1997 Dec
PMID:Pyrrolidine dithiocarbamate inhibits cytokine-induced VCAM-1 gene expression in rat cardiac myocytes. 945 Jun 60

The alpha4 chain (CD49d), which constitutes one of the chains of alpha4beta1 (very late activating antigen-4 [VLA-4]) and alpha4beta7 integrins, mediates migration of T cells to extravascular spaces. The interaction between VLA-4 and vascular cell adhesion molecule-1 (VCAM-1) has been shown to be the critical pathway for the selective accumulation of eosinophils and basophils at sites of allergic inflammation. T lymphocytes are also specifically recruited into allergic sites, including the allergic asthmatic airway. Increased numbers of activated CD4+ cells expressing the DR antigen subset of the human leukocyte antigens (HLA-DR) appear in the allergic lung 48 h after allergen inhalation. The mechanisms by which these cells localize into the lung are still unknown. We report that stimulation of allergen-specific T cells with allergen in vitro resulted in enhanced expression of alpha4 chain (CD49d) as measured by receptor density on allergen-specific T-cell lines and T-cell clones. Kinetic studies showed that CD49d density was enhanced over a 24- to 48-h period in a time-dependent fashion, and was coordinately upregulated with HLA-DR expression. We also demonstrated that increased expression of CD49d on T-cell lines 24 h and 48 h after stimulation correlated with increased adhesion to the CS-1 fragment of fibronectin. In contrast, lymphocyte function-associated antigen-1b (LFA-1b) (CD11b), LFA-3 (CD58), and intercellular adhesion molecule-1 (ICAM-1) (CD54) expression did not change with allergen stimulation. We also showed that CD49d receptor density on T cells obtained by bronchoalveolar lavage (BAL) of allergic patients before and 48 h after allergen challenge was significantly higher than that on T cells taken from BAL of normal subjects and from controls with other inflammatory lung diseases. Taken together, these findings indicate that allergen stimulation activates allergen-specific T cells and coordinately induces increased CD49d receptor expression and binding to counterligands. We postulate that allergen-driven upregulation of CD49d, which together with the beta1 chain constitutes VLA-4 integrin, may be responsible for the selective accumulation of T cells in the allergic asthmatic lung.
Am J Respir Cell Mol Biol 1998 Feb
PMID:CD49d expression and function on allergen-stimulated T cells from blood and airway. 947 17

Recent studies suggest that increased vascular cell adhesion molecule-1 (VCAM-1) expression on vascular endothelium in bronchial mucosa biopsies correlates with interleukin-4 (IL-4) levels in bronchiolar lavage fluid of allergic asthmatics. The severity of asthma in patients allergic to house dust mite has also been shown to correlate with lipopolysaccharide (LPS), rather than allergen, concentration in dust. We hypothesized that to induce effective VCAM-1 expression in human lung microvascular endothelial cells (HLMVEC), IL-4 may require the presence of a co-stimulus such as LPS. To test this hypothesis we measured, by enzyme-linked immunosorbent assay, induction of cell adhesion molecule expression on, and human eosinophil adhesion to, cultured HLMVEC monolayers pretreated with IL-4 alone or combined with LPS. IL-4 synergized with LPS to induce VCAM-1 expression at 24, 48, or 72 h, whereas IL-4 alone induced expression at 72 h only. IL-4 did not induce expression of intercellular adhesion molecule-1 or E-selectin or alter LPS-induced expression of either. Pre-exposure of HLMVEC to LPS or IL-4 (1 h), followed by IL-4 or LPS, respectively (23 h), also induced VCAM-1 expression. Eosinophil adhesion to HLMVEC monolayers treated with IL-4 and LPS together, but not alone, significantly (P < 0.001) increased from 9.6 +/- 1.5% (control) to 26.9 +/- 3.3% and was inhibited by a monoclonal antibody against the VCAM-1 ligand, very late antigen-4. Analysis of VCAM-1 mRNA revealed synergism between IL-4 and LPS which may, in part, contribute to enhanced VCAM-1 expression. These results suggest that the presence of a co-stimulus such as LPS may be necessary for IL-4 to effectively induce VCAM-1 expression in lung microvasculature.
Am J Respir Cell Mol Biol 1998 May
PMID:Interleukin-4 and lipopolysaccharide synergize to induce vascular cell adhesion molecule-1 expression in human lung microvascular endothelial cells. 956 32

A murine model of asthma is described in which we examined the role of intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of airway reactivity, pulmonary eosinophilia, and inflammation. We sensitized wild-type control [C57BL/6J, (+/+)] and ICAM-1 knockout [C57BL/6J-ICAM-1, (-/-)] mice to ovalbumin (OVA), and challenged them with OVA delivered by aerosol (OVA-OVA) to induce a phenotype consistent with an asthmatic response. Bronchial responsiveness to methacholine and counts of cell numbers and measurements of eosinophil content and cytokine levels in bronchoalveolar lavage fluid (BALF) were significantly attenuated in ICAM-1(-/-) mice as compared with (+/+) mice. We also showed that the absence of ICAM-1 had no significant affects on the production of serum IgE antibody, but did have an effect on ex vivo lymphocyte proliferation. Additionally, immunohistochemistry: (1) revealed increased staining for vascular cell adhesion molecule-1 (VCAM-1) after antigen challenge in the ICAM-1(-/-) mice but not in the ICAM-1(+/+) controls; and (2) confirmed the presence of alternatively spliced forms of ICAM-1 in the lungs of ICAM-1(-/-) mice. Thus, despite the availability of alternate adhesion pathways in ICAM-1(-/-) mice, the absence of ICAM-1 prevented eosinophils from entering the airways. In summary, we found that the ICAM-1 knockout mice exhibited a significantly inhibited response to aerosol antigen challenge for most of the parameters examined, and conclude that ICAM-1 is an important ligand mediating T-cell proliferation in response to antigen, eosinophil migration into the airways, and the development of airway hyperreactivity (AHR) in allergen-sensitized and -challenged mice.
Am J Respir Cell Mol Biol 1998 Jun
PMID:Reduction of antigen-induced airway hyperreactivity and eosinophilia in ICAM-1-deficient mice. 961 82

Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are members of the immunoglobulin superfamily adhesion molecules on vascular endothelium and important in the development of eosinophil (EOS) accumulation in allergic inflammation. To define the role of these adhesion proteins in EOS inflammation, peripheral blood EOS from allergic donors were incubated in either buffer (control)-, recombinant human (rh)-VCAM-1-, or rh-ICAM-1-coated plates, and the effects of these adhesion proteins on EOS effector functions were determined. VCAM-1 induced spontaneous EOS adhesion whereas EOS adhesion to ICAM-1 required a second signal, such as granulocyte macrophage colony-stimulating factor (GM-CSF). Although only VCAM-1 stimulated EOS superoxide anion (O2-) generation, the addition of GM-CSF (100 pM) to the reactions resulted in a greater and equivalent production of O2- with VCAM-1 and ICAM-1. In the presence of GM-CSF, ICAM-1 and VCAM-1 caused significant release of EOS-derived neurotoxin (EDN). Moreover, only ICAM-1 (no GM-CSF) promoted calcium ionophore A23187 (0.2 microM)-induced EOS leukotriene C4 (LTC4). Enhanced O2- generation, EDN release, and LTC4 generation observed with ICAM-1 and VCAM-1 were significantly inhibited by anti-beta2-integrin antibody. These results suggest that ICAM-1 and VCAM-1 are important in determining the eventual function of airway EOS.
Am J Respir Cell Mol Biol 1998 Jul
PMID:Granulocyte macrophage colony-stimulating factor augments ICAM-1 and VCAM-1 activation of eosinophil function. 965 Nov 92

A pulmonary Cryptococcus neoformans (Cne: strain 52D, ATCC24067) infection model in mice was used to examine the possible role for T cell-mediated immunity in regulating vascular adhesion molecules on lung endothelium during development of granulomatous inflammation. Resolution of pulmonary Cne infection in C.B-17 mice begins by Day 14 following intratracheal inoculation and depends on T cell-mediated recruitment of monocytes followed by their activation. C.B-17 scid/scid (SCID) mice mount a less exuberant pulmonary inflammatory response, recruit fewer monocytes into their lungs, and fail to clear the infection. Recruitment of leukocytes into infected tissue is mediated by both the interaction of adhesion molecules expressed on the surface of activated vascular endothelial cells with ligands on circulating cells, and the directed response of these leukocytes to chemotactic factors. The kinetics of expression of the endothelial cell adhesion molecules E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), all previously shown to regulate monocyte recruitment, were examined in the lungs of infected C.B-17 and SCID mice during pulmonary infection to determine if T cells were necessary for their upregulation. Immunohistochemical analysis showed that upregulation of E-selectin, VCAM-1, and ICAM-1 did not differ significantly between C.B-17 and SCID mice at any time during infection. Maximal expression in C.B-17 and SCID mice was noted between Days 5 and 7 for all three molecules and preceded maximal influx of leukocytes into the lung. Thus, the inability of SCID mice to recruit optimal numbers of monocytes into infected lungs was not the result of a failure to express the critical adhesion molecules early in infection, but likely reflected absence of immune dependent chemotactic factors.
Am J Respir Cell Mol Biol 1998 Oct
PMID:T and B cell independence of endothelial cell adhesion molecule expression in pulmonary granulomatous inflammation. 976 55

We investigated the in vitro effects of both prothymosin alpha1 (Pro alpha1) and transforming growth factor-beta1 (TGF-beta1) on the adhesion of peripheral blood lymphocytes (PBL) and on the expression of the adhesion molecules, endothelial-leukocyte adhesion molecule-1 (ELAM-1), intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on human umbilical vein endothelial cells (HUVECs). TGF-beta1 moderately but significantly decreased PBL-binding to interleukin-1 (IL-1)- stimulated HUVECs. However, Pro alpha1 in combination with TGF-beta1 completely restored the TGF-beta1 mediated effects. Other thymic peptides tested were ineffective. On HUVECs, TGF-beta1 diminished ICAM-1 and VCAM-1 expression, leaving ELAM-1 unchanged. Pro alpha1 in combination with TGF-beta1 showed no significant effects on ELAM-1 expression, but antagonized the TGF-beta1-induced decrease of ICAM-1 and VCAM-1 expression on activated HUVECs.
Int J Mol Med 1998 Apr
PMID:Prothymosin alpha1 antagonizes the inhibitory effects of transforming growth factor-beta1 on the adhesion of peripheral blood lymphocytes to human umbilical vein endothelial cells. 985 91

Advanced glycation endproducts (AGE) are supposed to increase endothelial expression of adhesion molecules like vascular cell adhesion molecule-1 (VCAM-1) by inducing an intracellular stress with subsequent activation of nuclear transcription factor NF-kappa-B. Quantitative analysis of VCAM-1-transcription has not been demonstrated concerning this topic. Thus, the aim of this study was to establish quantitative reverse transcription polymerase chain reaction (RT-PCR) assays using a spacer gene in order to measure the amounts of specific mRNA for VCAM-1 in human umbilical vein endothelial cells (HUVEC) which were stimulated with AGE-albumin (AGE-BSA). A recombinant RNA-standard was synthesized and used as internal RT-PCR standard. The amount of VCAM-1-mRNA in unstimulated HUVEC was found to be 2.2 +/- 2.7 copies per cell. After stimulation with AGE-BSA, mRNA-levels were elevated to 38.9 +/- 10.9 copies per cell. Positive controls (stimulated with lipopolysaccharide) revealed mRNA-levels of 78.7 +/- 27.5 copies per cell. We conclude that quantitative RT-PCR using the spacer gene technique is a valid and reliable method for the measurement of small amounts of specific
Int J Mol Med 1998 Oct
PMID:Establishment of a quantitative RT-pCR for detection of vascular cell adhesion molecule-1 transcripts in endothelial cells after stimulation with advanced glycation endproducts. 985 34


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