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 anti-inflammatory cytokine IL-10 is up-regulated in response to TNF-alpha suggesting a control mechanism of inflammation. In addition, we recently found systemic IL-10 release in response to acute stress reactions in the absence of any systemic inflammation. In vitro and in vivo studies in experimental models suggest that catecholamines induce IL-10 release via a cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) dependent pathway. Here we studied patients for plasma IL-10 after acute myocardial infarction, a very stressful event without significant signs of systemic inflammation. In fact, the activation of the sympathetic system initiated by cardiac infarction was accompanied by a temporary systemic release of IL-10. Catecholamine induced IL-10 may be released by different cells. Recently, we demonstrated that catecholamines directly stimulate the IL-10 promoter/enhancer via a cAMP/PKA pathway in monocytic cells. A cAMP responsive element (CRE) was identified as major target. Here we show that there is no influence of catecholamines on the IL-10 promoter activity in T-cells. In contrast to monocytic cells, in T-cells cAMP-induced PKA-dependent phosphorylation of the CRE-binding protein 1 (CREB-1) seems to play a marginal role in IL-10 induction, which was reflected by a low cAMP-dependent IL-10-promoter/enhancer stimulation in reporter gene assays. Thus, catecholamines are directly involved in the regulation of IL-10 expression in monocytic but not in T-cells after acute stressful conditions.
Mol Cell Biochem 2000 Sep
PMID:Catecholamines induce IL-10 release in patients suffering from acute myocardial infarction by transactivating its promoter in monocytic but not in T-cells. 1110 35

Spontaneous abortion of normal karyotype embryos in mice and in humans is associated with an increase in uterine T helper (Th) 1 type proinflammatory cytokines, tumour necrosis factor (TNF)-alpha, interferon-gamma and interleukin (IL)-1, and a deficiency of Th2/3 type cytokines, IL-4, IL-10, and transforming growth factor (TGF)-beta2. In mice, Th1 cytokines up-regulate a novel prothrombinase, fgl2, which via thrombin, leads to activation of polymorphonuclear leukocytes that terminate the pregnancy. Here we show that Th1 cytokines up-regulate fgl2 mRNA in fetal trophoblast and secondary decidua of CBA/JxDBA/2 and CBA/JxBALB/c matings, and promote fibrin deposition. This pattern is accompanied by a high rate of abortion. However, the spontaneous abortion rates in abortion-prone CBAxDBA/2 matings and in low abortion rate CBAxBALB/c matings were significantly lower than that expected from the frequency of implantations with high levels of fibrin and fgl2 mRNA(hi). As the glycoprotein OX-2 occurs in the pregnant rat uterus and can deviate cytokine responses to Th2/3, we investigated OX-2 in pregnant CBA/J mice. We found OX-2 mRNA was present at the same sites as fgl2 mRNA, but was reduced in response to Th1 cytokines. Furthermore, anti-OX-2 raised the abortion rate to predicted levels, while recombinant OX-2 dramatically reduced the abortion rate. Fgl2 prothrombinase may provide a mechanism explaining pregnancy loss, and conversely, successful pregnancy may be due in part to OX-2-dependent activation of maternal tolerance mechanisms at the feto-maternal interface.
Mol Hum Reprod 2001 Feb
PMID:Fgl2 prothrombinase expression in mouse trophoblast and decidua triggers abortion but may be countered by OX-2. 1116 Aug 45

Exquisitely regulated cytokine balance during early pregnancy is thought to be necessary for promoting survival of the fetal allograft. Our previous studies have demonstrated that membrane-bound human leukocyte antigen (mHLA-G) expressed on trophoblasts is one of the key factors in regulating cytokine balance by shifting the Th1/Th2 balance toward Th2 polarization, a favourable milieu for the maintenance of pregnancy. Given that trophoblasts secrete soluble HLA-G (sHLA-G), we examined its biological roles in comparison with mHLA-G. We cultured peripheral blood mononuclear cells (PBMC) with either the HLA-A and -B-deficient B lymphoblast cell line (721.221 cells) or the same cell line transfected with mHLA-G (721.221-G1 cells), in the presence or absence of recombinant sHLA-G. Cytokine concentrations in the culture media were determined by enzyme-linked immunosorbent assay. In contrast to mHLA-G protein, sHLA-G stimulated the release of tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma, whereas it reduced the release of interleukin (IL)-3, regardless of the presence of the presence of a stimulatory effect of the mHLA-G-expressing cells. Although mHLA-G reduced the release of IL-4, sHLA-G did not have any effect. Conversely, sHLA-G stimulated the release of IL-10 whereas mHLA-G was without effect. These results suggest that sHLA-G regulates the release of cytokines from PBMC chiefly by counterbalancing mHLA-G, and thereby may play a role in maintaining pregnancy.
Mol Hum Reprod 2001 Feb
PMID:Soluble HLA-G influences the release of cytokines from allogeneic peripheral blood mononuclear cells in culture. 1116 Aug 46

CD40-mediated interactions play an important role in the response to infections, transplantation, and cancer by affecting the development, activation, proliferation and differentiation of a variety of immune cells. In the current study we examined the role of CD40-mediated interactions in immune responses to bladder, pancreatic and breast carcinomas as well as melanoma cell lines using soluble human CD40L (rhCD40L) or anti-CD40 mAb in vitro. CD40 expression was readily detected in a large proportion of the cell lines and was augmented but not induced de novo by treatment with IFNgamma. Treatment of CD40-positive cell lines with rhCD40L or anti-CD40mAb enhanced cell surface expression of ICAM-1 and FAS and stimulated the production of IL-6, IL-8, GROalpha, GM-CSF and TNFalpha but not IL-4, IL-10, TGFbeta, MCP-1, RANTES, MIP-1beta, or IP-10. In addition, incubation of CD40+ tumour cell lines with immobilised rhCD40L or anti-CD40 mAb in vitro resulted in significant inhibition of proliferation and a corresponding decrease in viability. This CD40-mediated inhibition of cell growth was due, at least in part, to alterations in cell cycle and the induction of apoptosis. Transfection of CD40-negative tumour cell lines with the cDNA for CD40 conferred responsiveness to rhCD40L and anti-CD40 antibody. Finally, the presence of CD40 on the surface of carcinoma lines was found to be an important factor in the generation of tumour-specific T cell responses.
Mol Immunol 2000 Jun
PMID:Role for CD40-CD40 ligand interactions in the immune response to solid tumours. 1116 1

Alveolar macrophages are the preferential site for growth of Legionella pneumophila (Lp) during infection. However, the study of Lp infection in alveolar macrophages is difficult due to the limitation of available primary alveolar macrophages. In the present study, we established an in vitro Lp infection model in alveolar macrophages using a continuous cell line of murine alveolar macrophages designated MH-S. Infection of both MH-S cells and primary mouse alveolar macrophages obtained by alveolar lavage with virulent L. pneumophila (Lp-V) showed vigorous growth of the bacteria, but infection with avirulent L. pneumophila (Lp-Av) resulted in only minimum growth. Cytokine message expression determination in the MH-S cells after infection showed strong induction of interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha messages induced by Lp-V but minimal induction of these cytokines by Lp-Av infection. IL-1 alpha protein secretion and the message levels for IL-1 alpha were also analyzed, and remarkable induction of IL-1 alpha was evident in both macrophage types when infected with Lp-V. Analysis of IL-12 p40 responses of both macrophage types to Lp-V infection assessed by reverse transcriptase/polymerase chain reaction revealed induction of increased message levels, but significant levels were induced only slowly. Determination of IL-12 protein secretion by enzyme-linked immunosorbent assay of culture supernatants from both macrophage types infected with either Lp-V or Lp-Av showed only minimum production. Thus, MH-S alveolar macrophages showed a similar response to Lp infection compared with primary alveolar macrophages and can be a useful in vitro model system to study Lp infection. The study also revealed the restricted IL-12 protein secretion of alveolar macrophages by Lp infection.
Am J Respir Cell Mol Biol 2001 Mar
PMID:Alveolar macrophage cell line MH-S is valuable as an in vitro model for Legionella pneumophila infection. 1124 32

A monoclonal antibody (mAb), named TE-4F 10, was produced by fusing P3X-Ag8 myeloma cells with splenocytes of BALB/c mice immunized with a rat medullary thymic epithelial cell (TEC) line, (TE-R 2.5), previously established in our Institute. Flow cytometry showed that 85-95% TE-R 2.5 cells expressed the TE-4F10 antigen. The mAb immunoprecipitated a 29 kDa molecule from the TE-R2.5 cell lysate. Immunohistochemical analysis using single and double staining of the thymus with anti-cytokeratin (CK) mAb, showed that TE- 4F10 mAb selectively stains a subpopulation of medullary TEC. Hematopoietic and lymphoid cells were negative. The expression of the TE-4F10 antigen on TE-R 2.5 cells in vitro was significantly upregulated by interleukin 1 (IL-1) and tumor necrosis factor (TNFalpha). Other cytokines IL-4, IL-6, IL-10 and granulocyte - macrophage colony stimulating factor (GM-CSF) showed lesser stimulation on its expression, whereas interferon gamma (IFN) and dexamethasone were without significant effect. The TE-R 2.5 cell line strongly bound and induced apoptosis of a rat / mouse thymocyte heterohybridoma (BWRT8), phenotypically alphabetaTCRhiCD4hiCD8lo. TE-4F10 mAb significantly inhibited binding (40-50%) of both BWRT8 cells and the BWRT8 - MDP.1 subclone to TE-R 2.5 cells. The inhibition was enhanced when TEC were stimulated with IL-1 + TNFalpha. The mAb also significantly blocked apoptosis of BWRT8 but did not modulate cell death of the BWRT8 - MDP.1 subclone, which was resistant to TEC-induced apoptosis. These findings indicate that the TE-4F10 antigen might be selectively involved in adhesion and selection processes in the medullary thymic microenvironment. The mAb of the same characteristics has not been described so far.
Cell Mol Biol (Noisy-le-grand) 2001 Feb
PMID:Biochemical and functional characterization of a molecule expressed by a subset of thymic medullary epithelial cells. 1129 58

In this study we examined the effect of oral antigen (Ag) administration on the development of experimental asthma in different mouse strains. We selected BALB/c, BP2, CBA/Ca interleukin (IL)-5 transgenic, and BALB/c T-cell receptor-delta-deficient mouse strains because they exhibit different aspects of the asthma syndrome. Mice exposed to 1% ovalbumin (OVA), dissolved in the drinking water for 5 consecutive days, became unresponsive to subsequent immunogenic OVA challenges. This regimen of OVA administration induced Ag-specific unresponsiveness in all mouse strains tested, including gammadelta-deficient mice that are said to be resistant to tolerance induction. The Ag-specific unresponsiveness was characterized by reduced (almost absent) airway eosinophilic inflammation, airway hyperreactivity, and mucus production; also by low levels of T helper (Th) 2-type cytokines in bronchoalveolar lavage fluid, and decreased immunoglobulin (Ig) G1 and IgE OVA-specific antibody production. The unresponsive state was not associated with increased levels of the suppressive cytokines IL-10 and transforming growth factor (TGF)-beta or with immune deviation toward the Th1 pathway due to increased levels of interferon-gamma and IL-12. Moreover, treatment with anti- TGF-beta antibodies did not abrogate oral tolerance. Oral Ag administration was quite effective in suppressing the development of key features of asthma when initiated after primary immunization (Day 0) or after booster (Day 7), but not after challenge (Day 14) when it increased allergic responses. Collectively, our findings show for the first time the beneficial and detrimental effects of oral Ag administration on the development of experimental asthma.
Am J Respir Cell Mol Biol 2001 May
PMID:Suppression of asthma-like responses in different mouse strains by oral tolerance. 1135 Aug 18

We have previously shown that exposure of sensitized animals to lipopolysaccharide (LPS) 18 h after ovalbumin (OVA) challenge inhibits late-airway response (LAR). Using relatively selective nitric oxide synthase (NOS) inhibitors we have shown that LPS upregulates inducible NOS (iNOS) and downregulates constitutive NOS (cNOS) activity. In this study we set out to quantitate NOS isoenzyme activity in lung homogenates and to measure ex vivo interleukin (IL)-10 in tracheal explants of naive or sensitized and OVA-challenged rats exposed to LPS. iNOS activity was increased and cNOS activity reduced 6 h after LPS exposure in naive animals (n = 6, P < 0.001) and at 18 (n = 5, P < 0.001) or 24 (n = 5, P < 0.001) h after OVA challenge in sensitized animals. LPS exposure 18 h after OVA challenge in sensitized animals reversed OVA-induced changes in NOS isoenzyme activities (n = 5, P < 0.001). In naive animals IL-10 was increased 1 h after LPS exposure (n = 5, P < 0.001), peaked at 3 h (n = 9, P < 0.001), and remained elevated above baseline at 18 h (n = 11, P < 0.05). In sensitized animals, IL-10 was not increased until 18 h after OVA challenge (n = 11, P < 0.001). Due to the rapid IL-10 increase in naive animals the released IL-10 is likely to be preformed; however, in sensitized animals the results are consistent with de novo production of IL-10. In the sensitized and OVA-challenged group, exposure to LPS 18 h after OVA produced a 3-fold increase in IL-10 at 3 h after LPS exposure (n = 5, P < 0.001). The time course and kinetics of IL-10 release in those animals was similar to that seen in naive rats. These results support our previous conclusions on the basis of in vivo studies using isoenzyme inhibitors and have shown LPS to be able to reverse OVA-induced changes in NOS isoenzyme activities during an established LAR. LPS-induced release of IL-10 is thought to play an important immunomodulatory role in this model.
Am J Respir Cell Mol Biol 2001 May
PMID:Lipopolysaccharide inhibits the late-phase response to allergen by altering nitric oxide synthase activity and interleukin-10. 1135 Aug 36

The findings that bone marrow fibroblastoid stromal cells are important for activin A production prompted our investigation of activin A expression in fibroblast-like synoviocytes in joint capsule in this and previous studies. In the proliferative reactive synovial membrane obtained from rheumatoid arthritis patients, activin A is detected prominently in the fibroblastoid synovial cells, as well as in the smooth muscle and the endothelial layer of the arteries in these vascularized proliferative tissues. The concentration of activin A in the rheumatoid arthritis synovial fluid was 33.6+/-5.0 ng/ml, much higher than the activin A content of osteoarthritis fluid (10.0+/-1.1 ng/ml). Furthermore, our previous studies also showed that inflammatory cytokines, such as interleukin (IL)-1, transforming growth factor (TGF)-beta, interferon (IFN)-gamma, IL-8, and IL-10 markedly enhance the expression of activin A mRNA in synoviocytes. These findings are consistent with our studies in regard to the regulatory control of activin A production in bone marrow stroma and monocytes. In addition, the relationship of activin A to IL-6-induced biological activities in various cell types was also investigated. Although activin A has not been directly associated with inflammatory processes, future studies are needed to investigate its production in response to the accumulated levels of inflammatory cytokines in the synovium of the patients, as well as the quantitative differences in activin A concentrations in many patients with other inflammatory diseases.
Mol Cell Endocrinol 2001 Jun 30
PMID:Expression of activin A in inflammatory arthropathies. 1145 87

Immunization with specific proteins or peptides has been used to induce immunologic tolerance to allografts other than the lung. Recently, we have reported that the immune response to lung alloantigen also involves an immune response to type V collagen [col(V)]. The purpose of the current study was to determine if oral administration of col(V) to lung allograft recipients before transplantation downregulates acute rejection episodes. The data show that, compared with controls, col(V)-fed recipients had fewer polymorphonuclear cells and lymphocytes in allograft bronchoalveolar lavage fluid, and reduced rejection pathology. Data showing that col(V)- fed allograft recipients had diminished delayed-type hypersensitivity (DTH) responses to donor alloantigens suggest that feeding col(V) prevented allograft rejection by inducing tolerance to donor antigens. Systemic production of transforming growth factor (TGF)-beta, interleukin (IL)-4, or IL-10 has been reported to be a mechanism for oral tolerance-induced suppression of immune responses. Feeding col(V) induced upregulated production of TGF-beta, but not IL-4 or IL-10 in serum. Neutralizing TGF-beta recovered the DTH response to donor antigen in tolerant allograft recipients. Collectively, these data show that oral administration of col(V) is a novel approach to induce immunologic tolerance to lung allografts, and that TGF-beta contributed to suppression of the rejection response.
Am J Respir Cell Mol Biol 2001 Jul
PMID:Oral tolerance induction by type V collagen downregulates lung allograft rejection. 1147 72


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