Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) have been reported previously to mediate similar as well as antagonistic effects on murine macrophage functions. One effect common to both is the enhancement of tumour necrosis factor-alpha (TNF-alpha) secretion in macrophages. To assess further the effects of these two lymphokines on macrophage TNF-alpha production, we investigated the role of these lymphokines in the induction and stability of TNF-alpha messages along with interleukin-1 (IL-1) as a comparison. IFN-gamma and IL-4 increased lipopolysaccharide (LPS)-induced TNF-alpha, IL-1 steady-state message levels. In contrast to IL-1 messages, whose degradation was not significantly affected by either lymphokine, the stability of TNF-alpha messages differed after IFN-gamma and IL-4 treatment. Although IL-4 treatment increased the TNF-alpha transcription rate, an increase in the degradation rate of TNF-alpha mRNA in the IL-4-treated cells resulted in a lower level of steady-state mRNA than in the IFN-gamma-treated cells. Additionally, a 18,000 MW cytoplasmic factor was found to have specific binding activity to the AU-rich sequences of the TNF-alpha message in peritoneal macrophages. Although the binding activity of this factor was not affected by either IFN-gamma or IL-4, the binding of the factor to AU-rich sequences appeared to be important in the rapid degradation of TNF-alpha messages. Thus IFN-gamma and IL-4 may differentially affect the post-transcriptional control of TNF-alpha gene expression. And this lymphokine-mediated post-transcriptional control of the TNF-alpha gene does not appear to involve the alteration of binding activity of the 18,000 MW AU-rich sequence binding factor.
 ...
PMID:Differential regulation of tumour necrosis factor-alpha mRNA degradation in macrophages by interleukin-4 and interferon-gamma. 867 8

CD36 is an 88-kD integral membrane protein expressed on platelets, monocytes, macrophages, certain microvascular endothelia, and retinal pigment epithelium. It functions as an adhesive receptor for thrombospondin-1 (TSP-1), collagen, and malaria-infected erythrocytes and as a scavenger receptor for oxidized LDL and photoreceptor outer segments. The CD36-TSP-1 interaction plays a role in cell adhesion and the phagocytosis of apoptotic cells by macrophages. Because of the potential importance of the CD36-TSP-1 interaction in mediating atherogenic and inflammatory processes, we studied their expression in human peripheral blood monocytes exposed to soluble mediators known to regulate inflammation and atherogenesis. RNase protection assays showed 6- to 12-fold increases in CD36 mRNA in response to interleukin-4, monocyte colony-stimulating factor, and phorbol myristate acetate, while lipopolysaccharide and dexamethasone strongly downregulated CD36 mRNA. The downregulation of CD36 mRNA was associated with the disappearance of surface expression of CD36 antigen and loss of TSP-1 surface-binding capacity. Upregulation of CD36 mRNA was associated with a modest increase in surface antigen expression and a larger expansion of an intracellular pool of CD36. As with CD36, monocytes treated with monocyte colony-stimulating factor showed a rapid increase in TSP-1 mRNA expression. Moreover, while dexamethasone treatment decreased CD36 expression, it resulted in a rapid increase in TSP-1 mRNA, and while PMA increased CD36 mRNA, it rapidly decreased TSP-1 expression. Interferon gamma, which had no effect on CD36 mRNA, rapidly increased steady-state TSP-1 mRNA. Thus, expression of both CD36 and its ligand TSP-1 is regulated by soluble mediators, although certain mediators induce concordant changes and others discordant changes.
 ...
PMID:Regulation of monocyte CD36 and thrombospondin-1 expression by soluble mediators. 869 41

High levels of fibrinogen are recognized as an important vascular risk factor; however, it is not known if the increase of plasma fibrinogen is directly responsible for this risk, or is only a marker of vascular inflammation. To support this second hypothesis, Oncostatin M (OSM) is a potent stimulator of fibrinogen biosynthesis and induces smooth muscle cell proliferation. In the same way, we analysed whether interleukin-4 (IL-4), interleukin-10 (IL-10) or interleukin-13 (IL-13), which protect vessel walls from monocytes injuries leading to atherosclerosis, could influence fibrinogen biosynthesis. The two levels of regulation of fibrinogen biosynthesis were tested: firstly, the direct effect of these cytokines on fibrinogen production by the hepatoma cell line Hep G2, and secondly their effect on the secretion of hepatocyte stimulating factor (HSF) activity in the supernatant of lipopolysaccharide (LPS)-activated monocytes. IL-4 and IL-13 added to Hep G2 cells down-regulated both the increase of fibrinogen secretion induced by IL-6 and fibrinogen mRNA levels, this effect being more pronounced when Hep G2 were preincubated with the two cytokines before IL-6 addition. The effect of IL-10 was evidenced only on mRNA expression. IL-10 and IL-13 dose-dependently decrease HSF activity secreted by LPS-activated monocytes, whereas IL-4 had no effect. However, the three cytokines decreased HSF activity when monocytes were incubated with the cytokines before LPS activation. The effects of these cytokines on HSF activity are related to variations of IL-6 and OSM secretion. Our data strengthen the hypothesis that the fibrinogen level is a marker of vascular disease, since cytokines which have a protective vascular effect down-regulate fibrinogen production.
 ...
PMID:Down-regulation of fibrinogen biosynthesis by IL-4, IL-10 and IL-13. 870 33

We studied the potential role of B cells in T cell responses using severe-combined immunodeficient (SCID) mice grafted with the thymus from fetal C.B-17 mice (TG mice). These mice developed both CD4+ and CD8+ T cells, but not B cells within 2 months after transplantation. TG mice showed normal delayed-type hypersensitivity responses against the immunizing antigen ovalbumin (OVA). Lymph node (LN) cells of TG mice proliferated well in response to concanavalin A (Con A). Further, Con A stimulation induced the production of interleukin (IL)-2, IL-6 and interferon (IFN)-gamma and the expression of IL-4 mRNA. Thus, TG mice were reconstituted without remarkable immunodeficiency. However, these T cells failed to proliferate to OVA stimulation. Response to OVA was also inhibited in SCID mice grafted with fetal C.B-17 liver cells when B cells were depleted in the proliferation assay. Unresponsiveness against immunizing antigen was restored by the addition of antigen-primed B cells, but not by naive B cells, lipopolysaccharide-activated B cells or B cells primed with sheep red blood cells. Next, we examined whether antigen-primed B cells could induce T cell responses without professional antigen-presenting cells (APC). T and B cells were purified from OVA-immunized mice by cell sorter. These T cells proliferated in response to OVA and produced IFN-gamma in the absence of non-B APC. When anti-CD80 or anti-CD86 was added in the assay, proliferation and IFN-gamma production was inhibited. These results indicate that B cells activated specifically with antigen are required for the secondary response of T cells, but not for their priming.
 ...
PMID:Antigen-specific B cells are required for the secondary response of T cells but not for their priming. 876 71

Microglial cells function as regulators of immune reactivity within the CNS and may contribute to tissue injury under inflammatory conditions. Such functions are correlated with their state of activation. In this study, we report the de novo expression of CD14 by adult human CNS-derived microglia which acquire a bipolar activated morphologic phenotype in dissociated tissue culture. Surface CD14 expression can be down-regulated by interaction with its ligand lipopolysaccharide (LPS), and by the T-helper (Th1) cytokine interferon-gamma (IFN-gamma) or the Th2 cytokine interleukin-4 (IL-4). Semiquantitative polymerase chain reaction (PCR) analysis of CD14 mRNA expression under each condition suggests a different mechanism accounting for the reduced surface expression. LPS down-regulates CD14 mRNA, consistent with a feed-back signal preventing over-stimulation. IFN-gamma augments CD14 transcription, suggesting cleavage of surface CD14 consequent to general cell activation. IL-4 decreases mRNA production likely reflecting a generalized suppressive effect. The effect of LPS, IFN-gamma and IL-4 on CD14 expression differes from their effect on expression of the immune-accessory molecules B7-1 and HLA-DR, and on production of tumor necrosis factor-alpha (TNF-alpha), whose secretory pathway is similar to that of CD14. These results indicate the selective effects of molecules, likely to be present in the infected or inflamed CNS, on regulating CD14 expression and that there can be differential regulation of immune response relevant molecules expressed by activated microglia.
 ...
PMID:Regulation of CD14 expression on human adult central nervous system-derived microglia. 887 97

Leukoreduced allogeneic platelet transfusions have been previously shown to initially stimulate an in vitro cellular cytotoxicity and subsequently Induce the formation of immunoglobulin G (IgG) antidonor alloantibodies. To further characterize these responses and determine if they are related, recipient BALB/c H-2d mice were treated with aminoguanidine (AMG), a selective inhibitor of inducible nitric oxide synthase (iNOS), and transfused weekly with 2 x 10(8) C57BL/6 H2b platelets. In control, non-AMG-treated mice, transfusion significantly (P < .01) increased serum levels of interferon-gamma (IFN-gamma) by day 1 posttransfusion (PT). IFN-gamma returned to pretransfusion levels by day 3 PT, and its production was not affected by AMG treatment. Serum interleukin-4 (IL-4), on the other hand, was undetectable before and during the transfusion protocol. By day 3 PT, recipient spleen cells could mediate in vitro anti-P815 (auto), anti-EL4 (allo), and anti-R1.1 (third-party MHC) cytotoxicity, and these responses were maximal by day 7 PT. Concurrently, a significant reduction in the vitro ability of recipient splenocytes to respond to Concanavalin A (ConA) was observed; this was not seen with lipopolysaccharide (LPS) stimulation. Elevated levels of NO2- were found in the ConA culture supernatants from transfused mice at day 3 PT. Serum antidonor alloantibodies were detected by the fifth platelet transfusion. AMG treatment of recipient mice significantly inhibited the transfusion. Induced cytotoxicity and ConA-stimulated NO2- production, and restored ConA-induced proliferation to normal levels. AMG appeared to selectively inhibit platelet-induced alloantibody production in that it did not affect antibody production induced by transfusions with 10(5) allogeneic leukocytes or by immunization with a foreign protein antigen, human gamma globulin, in adjuvant therapy. These results indicate that an in vivo AMG-sensitive mechanism is essential for recipients to initiate a humoral IgG immune response against allogeneic platelets.
 ...
PMID:Recipient humoral immunity against leukoreduced allogeneic platelets is suppressed by aminoguanidine, a selective inhibitor of inducible nitric oxide synthase. 887 92

CD-1 mice intravenously infected with the virulent Brucella abortus 2308 strain simultaneously produce significant levels of gamma interferon (IFN-gamma) and interleukin-10 (IL-10) in their spleens between the second and eighth day post-infection with no production of interleukin-4 (IL-4). Endogenous synthesis of IL-10 does not affect the production of IFN-gamma in this organ, while the production of both cytokines during this period of time is accompanied by a statistically significant increase (P < 0.001) in the number of colony forming units (cfu) of B. abortus 2308 present in the organ. These findings suggest that although the endogenous synthesis of IL-10 apparently does not affect IFN-gamma production, it may affect the effector functions of macrophages to control intracellular brucellae. Production of the Th1 cytokine IFN-gamma during B. abortus 2308 infection is also associated with a specific IgG3 and IgG2a response against the B. abortus 2308 lipopolysaccharide (S-LPS) antigen.
 ...
PMID:Endogenous gamma interferon and interleukin-10 in Brucella abortus 2308 infection in mice. 888 Jan 35

Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional cytokine that promotes IgA/IgG2b switching and secretion. Here, we show a differential effect of TGF-beta 1 on Ig production by lipopolysaccharide-stimulated spleen and lymph node (LN) B cells. Exogenous TGF-beta 1 increased IgA production in B cell cultures and IgG2b production by spleen B cells. In contrast, IgG2b was suppressed by TGF-beta 1 in cultures of LN B cells, although endogenous TFG-beta was required for IgG2b production in LN B cell cultures. The suppressor properties of exogenous TGF-beta 1 (0.5 ng/ml) on IgG2b production by LN B cells were also seen when testing IgG1 or IgG2a induced by interleukin-4 or interferon-gama, respectively. These differences between B cells from each lymphoid tissue appeared to be related to a different TGF-beta antiproliferative effect, since proliferation of LN B cells was extremely sensitive to TFG-beta 1 and IgG2b production was more sensitive than IgA to the TFG-beta-mediated suppression. However, by counteracting the antiproliferative effect of TGF-beta 1 with a CD40 agonistic mAb (IC10), the IgG2b response by LN B cells was still lacking. IC10 was nevertheless inhibitory for IgG2b production in most cases, while increasing secretion of IgA in the very same cultures. Taken together, the results suggest that functional differences between spleen and LN B cells do exit, at least with regard to the immunomodulating properties of TGF-beta on both proliferation and Ig production. Moreover, functional differences exist between cells committed for IgA and IgG2b regarding their sensitivity to the antiproliferative activity of TGF-beta 1 and the effect of CD40-derived signals on Ig secretion.
 ...
PMID:Differential effects of transforming growth factor-beta 1 on IgA vs. IgG2b production by lipopolysaccharide-stimulated lymph node B cells: a comparative study with spleen B cells. 889 46

B and T cells present in the spleen and other sites of the immune system play a crucial role in the protection of individuals by mounting a specific primary and secondary immune response. Disturbances in their signaling and functioning could lead to a deterioration of the defense mechanisms and thereby lead to infections, pathologies or diseases. In this work, we studied the effects of stress on the protein synthesis and metabolism of mouse splenocytes. The study was done by radiolabeling the entire mouse with 35S-methionine (in vivo procedure) or by culturing spleen cells under various conditions of stimulation in the presence of 35S-methionine (in vitro labeling). The stimulus was lipopolysaccharide (LPS), LPS + interleukin-4 (IL-4) and concanavalin A (on A). Samples from immobilization stressed and control animals were studied in parallel. The results showed minimum alterations due to stress on B cells, though a small decrease in proliferative capacity was observed. In contrast, T cells are profoundly affected by stress. More than 100 new proteins are expressed on 2D-gel patterns of T cells from stressed animals as compared with controls, some of which could be implicated in different signaling, or could have appeared because of an alteration in a pathway of synthesis, or even as a consequence of a change in the composition of T cell populations induced by stress.
 ...
PMID:Lymphocyte protein synthesis: evidence that murine T cells are more affected by stress than B cells. 890 5

To study macrophage genes activated by lipopolysaccharide (LPS) we have constructed a cDNA library using the mouse macrophage cell line, RAW 264.7. By differential screening, a gene, designated LRG-21, was identified that showed nucleic acid sequence homology to rat liver regenerating factor-1 (LRF-1) and human activating transcription factor-3 (ATF3). Both LRG-21 and LRF-1 are transcribed within an hour following stimulation and in the absence of protein synthesis. The predicted protein sequence of LRG-21 consists of 181 amino acids with a molecular weight of 20.7 kDa. All three sequences contain basic and leucine zipper regions characteristic of the c-Fos and c-Jun family of transcription factors, but the remainder of the sequences are unrelated to this family. Recombinant LRG-21 has been shown to bind to a phorbol ester promoter element. Additional experiments have shown that LRG-21 is also induced by interferon-gamma (IFN-gamma) and by interleukin-4 (IL-4) in both RAW264.7 cells and murine peritoneal macrophages. Based on these observations, it is likely that LRG-21 plays an important role in macrophage activation.
 ...
PMID:Identification of a lipopolysaccharide inducible transcription factor in murine macrophages. 896 Jan 23


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