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

CD5 expression on B cells is regulated by certain humoral factors. In a pre-B leukemia cell line 70Z/3, we found that interleukin 4 down-regulates it. Herein, we report that zinc influences spontaneous CD5 expression by this cell line as well as actions of these factors on CD5 expression considerably. In zinc-depleted culture media, spontaneous CD5 expression by 70Z/3 cells was enhanced. In contrast, the down-regulatory action of interleukin 4 was significantly reduced under culture conditions of zinc depletion. The supplementation of zinc to physiologic concentrations (1 to 2 microM) abolished such effects of zinc-depleted medium. The reduction of the suppressive action of interleukin 4 was observed at the level of gene expression. However, CD5 mRNA expression enhanced by lipopolysaccharide or NZB-SF was not further enhanced under conditions of zinc deficiency. These observations may suggest that CD5 expression by malignant or even normal B cells may be influenced by cellular/serum zinc levels.
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PMID:Zinc depletion modifies CD5 expression by 70Z/3 murine pre-B leukemia cell line. 171 63

The 52 kD myeloid membrane glycoprotein CD14 represents the receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein (LBP); it is involved in LPS induced tumor necrosis factor-alpha production. Expression of CD14 increases in monocytes differentiating into macrophages, and it is reduced by rIFNg in monocytes in vitro. In the present study CD14 membrane antigen expression was investigated in cultures of human mononuclear leucocytes (PBL), in elutriated, purified monocytes, and in blood monocyte derived Teflon cultured macrophages. Cells were incubated for 15 or 45 h with rIL-1, rIL-2, rIL-3, rIL-5, rIL-6, rTNFa, rGM-CSF, rM-CSF, rTGFb1, rIFNa, lipopolysaccharide (LPS), and, as a control, rIFNg. The monoclonal antibodies Leu-M3 and MEM 18 were used for labelling of CD14 antigen by indirect immunofluorescence and FACS analysis of scatter gated monocytes or macrophages. IFNg concentrations were determined in PBL culture supernatants by ELISA. rIFNa and rIL-2 reduced CD14 in 15 and 45 h PBL cultures, an effect mediated by endogenous IFNg, since it was abolished by simultaneous addition of an anti-IFNg antibody. rIFNa and rIL-2 were ineffective in purified monocytes or macrophages. rIL-4 strongly reduced CD14 in PBL and purified monocytes after 45 h, whereas in macrophages the decrease was weak, although measurable after 15 h. The other cytokines investigated did not change CD14 antigen expression. Cycloheximide alone reduced CD14, but when added in combination with rIFNg the effect on CD14 downregulation was more pronounced. The effect of rIFNg on CD14 in PBL cultures was dose-dependently inhibited by rIL-4 and this inhibition is probably due to an IL-4 mediated blockade of IFNg secretion. LPS at a low dose increased CD14, at a high dose it produced a variable decrease of CD14 in PBL, which was probably due to LPS induced IFNg secretion. LPS strongly enhanced CD14 in 45 h cultures of purified monocytes. The results, showing that CD14 antigen expression is upregulated by LPS and downregulated by rIFNg and rIL-4, suggest that the LPS-LBP receptor is involved in the feedback response of IFNg and IL-4 to LPS stimulation.
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PMID:Effect of cytokines and lipopolysaccharide on CD14 antigen expression in human monocytes and macrophages. 172 47

An antisense phosphorothioate (S)-oligonucleotide to a sequence in the intervening (I) region of the gamma 2b immunoglobulin (Ig) heavy chain gene inhibits Ig secretion by B cells stimulated with lipopolysaccharide (LPS) or LPS plus interleukin 4. It is also a striking stimulant of DNA synthesis by resting B cells. The antisense S-oligonucleotide causes a 10-20-fold increase in the expression of the gamma 2b germline transcript. Among mutants of the antisense S-oligonucleotide, some show all the effects whereas others are inactive. A similar hierarchy exists in the quantitative biological activities of mutant S-oligonucleotides and in their capacity to hybridize to the sense oligonucleotide, strongly suggesting that an I gamma 2b sequence in the RNA transcript or in the noncoding strand of the DNA is the target of the antisense S-oligonucleotide. The possible relationship of the overexpression of the germline gamma 2b transcript to the biological functions of the I gamma 2b antisense S-oligonucleotide is discussed.
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PMID:An antisense oligonucleotide complementary to a sequence in I gamma 2b increases gamma 2b germline transcripts, stimulates B cell DNA synthesis, and inhibits immunoglobulin secretion. 173 18

Phagocytosis of Giardia lamblia trophozoites by cytokine-activated and non-activated bone marrow-derived macrophages was examined in vitro. Macrophages treated with recombinant interferon-gamma (IFN-gamma) and bacterial lipopolysaccharide (LPS) ingested a significantly higher number of in vitro-grown trophozoites than untreated macrophages. Maximal uptake of parasites occurred after 4 h and 6 h of incubation where 81.4% and 79.1% of macrophages were positive for trophozoites. Other cytokines tested, IL-2, IL-3, IL-4, IL-5, GM-CSF, CSF-1 and tumour necrosis factor-alpha (TNF-alpha) either alone or in combination with LPS, failed to activate macrophages to phagocytose G. lamblia. The induction of this activated macrophage anti-microbial function was achieved pharmacologically using phorbol myristate acetate (PMA) and ionophore A23187. The giardicidal activity of macrophages activated with IFN-gamma and LPS or that induced by PMA and A23187 was inhibited by H-7, indicating the role for protein kinase C in the intracellular events following activation.
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PMID:Phagocytosis of Giardia lamblia trophozoites by cytokine-activated macrophages. 173 94

Rat salivary gland culture supernatants (SGSN) were shown to inhibit the proliferation of rat spleen cells induced by the mitogens concanavalin A (ConA), phytohaemagglutinin (PHA), pokeweed mitogen (PWM), lipopolysaccharide (LPS) and S. typhimurium mitogen (STM). The responses of B cells were more markedly inhibited than the responses of T cells. Factors contained in SGSN which had a molecular weight smaller than 3500 inhibited all responses, whereas factors greater than 3500 only inhibited responses induced by PWM, LPS or STM. Factors present in SGSN also inhibited the proliferation of two B cell hybridoma cell lines, as well as the IL-2-responsive cell line CTLL-2 and the IL-4-responsive cell line CT.4S. However, SGSN factors having a molecular weight greater than 3500 did not inhibit CTLL-2 proliferation. These data indicate that rat salivary glands contain factors which differentially regulate T and B cell proliferative responses in vitro and which may modulate localized immune responses in the salivary gland in vivo.
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PMID:Modulation of T and B cell proliferative responses by factors present in rat salivary glands. 175 18

Our previous work demonstrated that chimeric immunoglobulin mRNAs (trans-mRNAs) composed of a transgenic VHDJH region and endogenous CH sequences could be synthesized, most likely by a trans-splicing mechanism, in a transgenic line carrying a rearranged human membrane-type mu chain gene. In this study we further investigated regulation of trans-mRNA expression. Regulated expression of different gamma subclasses of trans-mRNA was similar to that of class switching: IL-4 together with lipopolysaccharide (LPS) predominantly increased the amount of gamma 1 trans-mRNA whereas LPS alone mainly induced gamma 3 and gamma 2b trans-mRNAs. Expression of the gamma class trans-mRNAs was preceded by germline transcription from the corresponding CH genes, but the co-existence of such germline transcripts and transgene transcripts was not sufficient for trans-mRNA production. Transforming growth factor-beta induced germline transcripts of the alpha chain CH gene but had no obvious effects on alpha trans-mRNA induction. Both C alpha gene alleles were used in trans-mRNA but in different frequencies. We could also detect trans-mRNA expression in another transgenic mouse line which carries a rearranged mouse VHDJH-C mu gene. These results indicate that trans-mRNA synthesis is not restricted to either a particular transgenic line or an isotype, but is a general mechanism to express a second isotype with the VH regions of rearranged mu chain transgenes.
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PMID:Regulated expression of immunoglobulin trans-mRNA consisting of the variable region of a transgenic mu chain and constant regions of endogenous isotypes. 177 16

The murine suppressive factor of allergy (SFA) has been purified from a T-cell hybridoma and found to consist of two functionally and biochemically distinct protein molecules. One protein (17 kDa) modulates the low-affinity Fc receptor for IgE on lymphocytes (i.e., CD23); it decreases the binding avidity of IgE to CD23-bearing B cells without affecting quantitative expression of CD23 and is thus designated epsilon-receptor-modulating protein. The second protein (30 kDa) suppresses IgE biosynthesis (i.e., SFA). This purified SFA suppresses interleukin 4-induced IgE and IgG1 synthesis by lipopolysaccharide-activated spleen cells but has no effect on other antibody isotypes; since the activity of SFA is not blocked by anti-interferon gamma monoclonal antibody, it is thus distinct from interferon gamma. The data presented indicate that epsilon-receptor-modulating protein and SFA are protein molecules that are involved in modulating the CD23 molecule and IgE antibody synthesis, respectively.
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PMID:Purification of murine suppressive factor of allergy into distinct CD23-modulating and IgE-suppressive proteins. 182 84

Chronic fatigue syndrome (CFS) is an idiopathic illness associated with a variety of immunologic abnormalities. To investigate potential pathogenetic mechanisms, we evaluated serum levels and peripheral blood mononuclear cell (PBMC) production of selected cytokines and immunoglobulins. Serum bioactive transforming growth factor beta (TGF-beta) levels were higher (P less than 0.01) in patients with CFS (290 +/- 46 pg/mL) than in control subjects (104 +/- 18 pg/mL), but levels of other cytokines tested were not different. Lipopolysaccharide-stimulated release of interleukin 1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha was increased (P less than 0.05) in PBMC cultures from patients with CFS versus control subjects; enhanced (P less than 0.01) IL-6 release to phytohemagglutinin was also observed. In contrast, TGF-beta release in response to lipopolysaccharide was depressed (P less than 0.01) in PBMC cultures derived from patients with CFS. No differences in IL-2 and IL-4 or immunoglobulin production were observed. The enhanced release of inflammatory cytokines by stimulated PBMC from patients with CFS suggests that these cells are primed for an increased response to immune stimuli. These data also suggest an association between abnormal regulation of TGF-beta production in vivo and in vitro with the immunologic consequence of CFS.
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PMID:Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome. 187 78

Mouse macrophages infected with Trypanosoma cruzi in vitro may be activated to reduce parasite infection by interferon gamma (IFN-gamma). The addition of up to 10,000 units of IFN-gamma however, does not result in a 100% reduction of intracellular parasites. We, therefore, investigated the possibility that macrophages require an additional signal or signals to completely clear T. cruzi infection. Because the combination of IFN-gamma with lipopolysaccharide greatly enhanced macrophages ability to decrease the number of intracellular parasites, the interaction of IFN-gamma with tumor necrosis factor (TNF) was examined. TNF alone and the combination of TNF with IFN-gamma did not have a significant effect on reducing parasite numbers below that obtained with IFN-gamma alone. This was also true for lymphotoxin, a lymphokine similar to TNF in structure and function. The effect of IFN-gamma in combination with a cytokine-rich supernatant containing IL-2, IL-3, IL-4, IL-5, and IFN-gamma on macrophage clearance of the parasite was also examined. The cytokine-rich supernatant alone had no effect on reducing parasite infection of the macrophages; indeed, in some experiments the addition of the supernatant resulted in an increase in the level of parasite infection. However, 1000 units of IFN-gamma combined with the complex cytokine mixture caused a decrease in parasite infection of nearly 100% compared to that of control cultures treated with media alone. To determine which cytokine or cytokines in the supernatant were responsible for this synergistic activity, anti-cytokine antibodies were added to the supernatant prior to its addition with IFN-gamma to the cultures. Anti-IL-4 was the only antibody found to inhibit the synergism of IFN-gamma with the cytokine-rich supernatant. IL-4, however, did not significantly enhance the ability of IFN-gamma to induce macrophage clearance of the parasite, and IL-4 alone caused a slight increase in parasite infection in vitro. These results further define the role that cytokines play in T. cruzi infection of macrophages in vitro and suggest that the interaction of cytokine networks within this system is complex.
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PMID:Trypanosoma cruzi: cytokine effects on macrophage trypanocidal activity. 190 95

We analyzed the molecular mechanism for the immunoglobulin (Ig) multiple isotype expression using a transgenic mouse (TG.SA) model system. Though most of the endogenous mu chain expression was excluded by the expression of the human rearranged mu transgene in the TG.SA mouse, a significant portion of splenic B lymphocytes could express the transgenic human IgM and endogenous mouse IgG simultaneously after stimulation with lipopolysaccharide and interleukin 4. The fluorescence-activated cell sorter-purified population of the human IgM+/mouse IgG+ cells expressed mRNA that consisted of properly spliced sequences of the transgenic VHDJH and the endogenous mouse C gamma genes (trans-mRNA), together with the transgenic human mu mRNA and germline transcripts of the mouse C gamma gene, without apparent rearrangement of the transgene. We also found that a lymphoma tumor, derived from the cross between the TG.SA mouse and another transgenic mouse carrying Ig H chain enhancer-driven c-myc oncogene, expressed about equal levels of the trans-mRNA and the transgenic mu mRNA without DNA rearrangement in either the transgene or the endogenous mouse switch region. These findings strongly support our previous proposal that the trans-splicing can account for the multiple isotype expression in this transgenic model and also suggest that novel molecular mechanism(s) might be involved in this reaction.
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PMID:Trans-splicing as a possible molecular mechanism for the multiple isotype expression of the immunoglobulin gene. 190 29


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