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)

To identify genes induced during macrophage activation, a cDNA library was prepared from cultures of the RAW 264.7 mouse macrophage cell line that had been treated with conditioned medium from mitogen-stimulated spleen cells, and the cDNA library was screened by differential plaque hybridization. Eleven cDNA clones, designated CRG-1 through CRG-11, corresponding to mRNA species inducible in RAW 264.7 cells by the spleen cell conditioned medium, were isolated. Inductions were not blocked by cycloheximide. All of the mRNAs were inducible by gamma interferon, and some were also inducible by alpha and beta interferons, by lipopolysaccharide, by phorbol 12-myristate 13-acetate, and by the calcium ionophore A23187. Sequencing of the cDNAs revealed that CRG-1, CRG-3, and CRG-5 are cDNAs of recently identified transcription factors IRF-1, zif/268, and LRF-1 respectively. As previously reported, CRG-2 and CRG-10 (MIG) encode new members of the platelet factor 4 family of cytokines. CRG-6 corresponds to a new member of a family of interferon-inducible genes clustered on mouse chromosome 1, CRG-9 corresponds to a prostaglandin synthase homolog, CRG-8 corresponds to beta 2-microglobulin, and CRG-4 corresponds to metallothionein II. CRG-11 contains sequences of a truncated L1Md repetitive element as well as nonrepetitive sequences. The nonrepetitive sequence of CRG-11 as well as the sequences of CRG-7 are not closely related to published sequences. The CRG genes and proteins are of interest because of their involvement in macrophage activation, because of their roles as mediators of the effects of gamma interferon and other pleiotropic agents, and because of their usefulness as tools for studying the signal pathways through which gamma interferon and other inducers exert their effects on gene and protein expression.
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PMID:A collection of mRNA species that are inducible in the RAW 264.7 mouse macrophage cell line by gamma interferon and other agents. 137 86

In order to identify novel proteins produced by activated macrophages, a cDNA library was made from cultures of the mouse macrophage-like cell line RAW 264.7 that had been treated with conditioned medium from mitogen-stimulated spleen cells, and the library was screened by differential plaque hybridization. A cDNA clone was isolated that detected a 1.4-kilobase mRNA that accumulated dramatically in response to the spleen cell conditioned medium. The 1.4-kilobase mRNA encodes a predicted protein of 98 amino acids, designated CRG-2, molecular weight (Mr) 10,781, with a 21-residue signal peptide. The amino acid sequence indicates that CRG-2 is a member of the platelet factor 4 family (PF4) of cytokines. The CRG-2 mRNA was induced by alpha-, beta-, and gamma-interferons (IFNs) and by lipopolysaccharide. In response to IFN-gamma, the CRG-2 mRNA level reached a peak between 3 and 6 h. The accumulation of CRG-2 mRNA was not blocked by cycloheximide. Among the known members of the PF4 family, CRG-2 is most closely related to the interferon-inducible human protein IP-10. The 5'-flanking region of the crg-2 gene was isolated, and comparisons between crg-2 and IP-10 genes, mRNAs, and proteins reveal conserved features of possible functional importance. CRG-2 may play a role in host defense, particularly in the response to viral infection.
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PMID:Identification of CRG-2. An interferon-inducible mRNA predicted to encode a murine monokine. 211 20

We previously reported the isolation and characterization of cDNA clones encoding novel lipopolysaccharide (LPS)-inducible mRNAs from murine peritoneal macrophages. We now present the complete coding sequence of a cDNA previously termed D3. Analysis of multiple clones from a murine macrophage cDNA library provided a complete cDNA sequence of approximately 1.6 kb. The corresponding RNA contains a single open reading frame encoding a hydrophilic protein composed of 425 amino acids and is characterized by a region including three perfect and two imperfect repeats of a seven-amino-acid sequence. Based on nucleotide and deduced amino acid sequence, this mRNA is a new member of a previously described multigene cluster of interferon-inducible genes termed the Mouse 200 series genes. This new sequence most closely resembles gene 204 because both D3 and 204 genes have segments containing the seven-amino-acid repeat sequence. The Mouse 202 and 204 genes, however, have an approximately 200-amino-acid carboxyl-terminal domain that is absent in the LPS-inducible macrophage-derived cDNA. In addition, D3, 202, and 204 can all be distinguished from one another by virtue of unique 3' noncoding regions 200-300 base pairs in length. The D3 unique sequence is largely restricted to the smallest of the three size classes of this gene family expressed in macrophages and is not detected in interferon- or platelet-derived growth factor-stimulated fibroblasts. Overall, three separate mRNAs have now been described, each of which has three or more of a possible seven nucleotide sequence domains. Although the function(s) of the members of this gene family remains unknown, the multiple forms inducible by diverse stimuli and their restricted cell type expression suggest diverse and important physiologic roles for their products in inflammation.
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PMID:A lipopolysaccharide-inducible macrophage gene (D3) is a new member of an interferon-inducible gene cluster and is selectively expressed in mononuclear phagocytes. 768 66

In a search for glucocorticoid attenuated response genes (GARGs) induced by lipopolysaccharide (LPS) in murine Swiss 3T3 cells, we cloned 12 GARG cDNAs (J. B. Smith and H. R. Herschman, 1995, J. Biol. Chem. 270, 16756-16765). Analysis of complete cDNA sequences indicates that three of these genes encode members of a highly conserved family of proteins containing multiple tetratricopeptide repeat (TPR) domains. GARG-16 is a homologue of the interferon-induced human IFI-56K gene. GARG-39 is a homologue of the interferon-induced human ISG-54K and hamster CL-54K genes. The predicted GARG-49/IRG2 protein is 60-75 amino acids shorter than other known members of this gene family, and its carboxyl-terminal half is relatively divergent. Homologues of GARG-49/IRG2 in other species have not been reported. The predicted GARG-16 and GARG-39 proteins, and their homologues, contain 10 TPR domains. GARG-49/IRG2 shares the first 6 domains and part of the 7th, but lacks domains 8,9, and 10. Message levels of GARG-16, GARG-39, and GARG-49/IRG2 are increased by LPS stimulation in Swiss 3T3 cells and in peritoneal macrophages. Unlike many primary response genes, these three genes are not induced by serum stimulation in Swiss 3T3 cells. All three are induced in the RAW 264.7 macrophage cell line by LPS, by interferons-alpha/beta, and by interferon-gamma. Despite these similarities, quantitative differences in their responses to different stimuli indicate that GARG-16, GARG-39, and GARG-49/IRG2 are regulated independently. We speculate that the proteins encoded by these LPS- and interferon-inducible genes may participate in multicomponent assemblies via their TPR domains.
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PMID:The glucocorticoid attenuated response genes GARG-16, GARG-39, and GARG-49/IRG2 encode inducible proteins containing multiple tetratricopeptide repeat domains. 866 Jun 59

Signal transduction through Toll-like receptors (TLRs) originates from their intracellular Toll/interleukin-1 receptor (TIR) domain, which binds to MyD88, a common adaptor protein containing a TIR domain. Although cytokine production is completely abolished in MyD88-deficient mice, some responses to lipopolysaccharide (LPS), including the induction of interferon-inducible genes and the maturation of dendritic cells, are still observed. Another adaptor, TIRAP (also known as Mal), has been cloned as a molecule that specifically associates with TLR4 and thus may be responsible for the MyD88-independent response. Here we report that LPS-induced splenocyte proliferation and cytokine production are abolished in mice lacking TIRAP. As in MyD88-deficient mice, LPS activation of the nuclear factor NF-kappaB and mitogen-activated protein kinases is induced with delayed kinetics in TIRAP-deficient mice. Expression of interferon-inducible genes and the maturation of dendritic cells is observed in these mice; they also show defective response to TLR2 ligands, but not to stimuli that activate TLR3, TLR7 or TLR9. In contrast to previous suggestions, our results show that TIRAP is not specific to TLR4 signalling and does not participate in the MyD88-independent pathway. Instead, TIRAP has a crucial role in the MyD88-dependent signalling pathway shared by TLR2 and TLR4.
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PMID:Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4. 1244 41

We have analyzed the gene expression profile of monocytes in response to a highly purified cell wall fraction of Mycobacterium bovis BCG, a clinically approved adjuvant known as BCG cell wall skeleton (BCG-CWS). It is composed of mycolic acid, arabinogalactan, and peptidoglycan and confers Toll-like receptor 2 (TLR2)- and TLR4-dependent signaling that induces monocytes to differentiate into antigen-presenting cells (APCs). Here we report differential gene expression analysis with BCG-CWS-stimulated versus nonstimulated monocytes. BCG-CWS exerted massive induction of genes regulated by TLR signaling. Marked gene regulatory characteristics in BCG-CWS-stimulated cells compared to lipopolysaccharide (LPS)-stimulated cells follow. (i) Spliced mRNAs encoding soluble forms of TREM-1 and TREM-2 (recently discovered inflammatory-signal-amplifying receptors) were regulated by BCG-CWS, resulting in their differential expression. (ii) The genes for zinc-iron transporter protein (ZIP)-like family proteins HKE-1 and LIV-1 were induced exclusively by BCG-CWS. (iii) Interleukin-23 (IL-23), rather than IL-12p70, was induced by BCG-CWS, while interferon-inducible genes were induced only by LPS. By Northern and reverse transcription-PCR analyses, we confirmed the differential expression of more than 30 BCG-CWS regulatory genes, and their expression was compared with that of LPS and other known TLR ligands. A battery of genes responded rapidly and for a short time to LPS but for a long time to BCG-CWS. Structural analysis of the identified novel or hypothetical proteins revealed that some are potential candidates as signaling mediators or transcriptional regulators. Hence, BCG-CWS may profoundly modulate APC responses in a way distinct from that of LPS, leading to possible advantages for its adjuvant-active therapeutic potential.
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PMID:Mycobacterium bovis BCG cell wall-specific differentially expressed genes identified by differential display and cDNA subtraction in human macrophages. 1474 39

We describe the cloning and expression of the mouse gene interferon-inducible-protein 15 (IP15), whose activation is related to the acute phase of experimental pancreatitis. Analysis of its structure indicates that it encodes a putative transmembrane protein of 137 amino acids. This gene contains a predicted IFN-stimulable-response element. In vivo studies showed that IP15 is strongly activated in pancreas early during caerulein-induced pancreatitis. In situ hybridization of IP15 mRNA showed that its expression is restricted to acinar cells. IP15 was also induced in pancreas under systemic-lipopolysaccharide treatment and in intestine under Salmonella infection. In vitro studies using NIH3T3 fibroblasts showed that IP15 is induced by IFN-alpha. Growth rate was significantly lower in cells transfected with pcDNA4/IP15 plasmid. In addition, cells expressing IP15 showed less capacity to develop colonies after antibiotic selection. In conclusion, we identified a new interferon-inducible gene that is activated early in pancreas with pancreatitis and whose expression inhibits cell growth.
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PMID:Cloning of IP15, a pancreatitis-induced gene whose expression inhibits cell growth. 1518 81

Adjuvants induce the expression of a number of genes in dendritic cells (DCs), which facilitate effective antigen-presentation and cytokine/chemokine liberation. It has been accepted that the toll-like receptor (TLR) family governs the adjuvant activity in DCs. An adjuvant with a long history is mycobacteria in an oil-in-water emulsion, namely Freund's complete adjuvant. Since the active center for the adjuvancy in mycobacteria is the cell-wall skeleton (CWS), we used the bacillus Calmette-Guerin cell-wall skeleton (BCG-CWS) to test DC maturation by GeneChip analysis. We identified the genes supporting an efficient DC response and output. Approximately 2000 genes were up-regulated by BCG-CWS stimulation. BCG-CWS-, peptidoglycan (PGN)- and lipopolysaccharide (LPS)-stimulation generally up-regulated some gene clusters including genes for inflammatory cytokines (TNF, IL1alpha, IL1beta, IL6, IL12 p40, IL23 p19, etc.), chemokines (CCL20, IL8, etc.), cell adhesion molecules (ICAM-1, etc.), apoptosis-related proteins (GADD45B, BCL2A1, etc.), metabolic enzymes (PTGS2, SOD2, etc.) and miscellaneous proteins (EHD1, TNFAIP6, etc.). LPS-stimulation, but not BCG-CWS- or PGN-stimulation, up-regulated the interferon-inducible antiviral proteins, including IFIT1, IFIT2, IFIT4, CXCL10, ISG15, OASL, IFITM1 and MX1. We also found that the BCG-CWS- or PGN-stimulation up-regulated CXCL5, MMP1, etc. We discussed their properties in association with TLRs and recently discovered TLR adapters.
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PMID:Gene-inducing program of human dendritic cells in response to BCG cell-wall skeleton (CWS), which reflects adjuvancy required for tumor immunotherapy. 1586 Feb 29

Alcohol abuse impairs the pulmonary immune response to infection and increases the morbidity and mortality of bacterial pneumonia. Acute alcohol intoxication suppresses lung expression of CXC chemokines bearing the Glu-Leu-Arg motif (ELR+) following lipopolysaccharide (LPS) challenge, but its effect on the structurally related ELR- CXC chemokines, which attract T cells, is unknown. We therefore investigated the effect of acute alcohol intoxication on the pulmonary response to intratracheal (i.t.) LPS challenge for the ELR- CXC chemokines monokine induced by gamma (MIG or CXCL9), interferon-inducible protein 10 (IP-10 or CXCL10), and interferon-inducible T cell alpha chemoattractant (I-TAC or CXCL11). Male C57BL/6 or C3H/HeN mice were given an intraperitoneal injection of ethanol (3.0 g/kg) or phosphate buffered saline 30 min before i.t. LPS challenge. Chemokine mRNA transcripts were measured at 0, 2, 6, and 16 h. Acute alcohol intoxication inhibited the lung's expression of all three chemokine genes in response to LPS. Lung IFN-gamma mRNA was also inhibited by acute intoxication over the same time course. The in vitro effect of ethanol on chemokine secretion was further studied in the MH-S alveolar macrophage cell line. IP-10, MIG, and I-TAC in response to LPS were enhanced by exogenous interferon (IFN)-gamma, and these responses were blunted by exposure to ethanol. Alcohol exposure did not affect MH-S cell nuclear factor kappa beta p65 nuclear localization during challenge, despite dose-dependent inhibition of Erk 1/2 phosphorylation. In addition, phospho-signal transduction and activator of transcription 1 was not decreased in the presence of acute ethanol, thereby indicating that acute intoxication does not affect IFN-gamma signaling in MH-S cells. Recruitment of CD3+ T cells into the alveolar space 4 days after LPS challenge was moderately impaired by acute ethanol intoxication. These results implicate acute ethanol intoxication as a significant inhibitor of lymphocyte chemoattractant expression during pulmonary inflammation.
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PMID:Acute alcohol intoxication suppresses the pulmonary ELR-negative CXC chemokine response to lipopolysaccharide. 1788 9

Toll-like receptors (TLRs) play an important role in host defense by sensing invading microbial pathogens and initiating innate immune responses. The stimulation of TLRs by microbial components triggers the activation of myeloid differential factor 88 (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing interferon-beta (TRIF)-dependent downstream signaling pathways. Isoliquiritigen in (ILG), an active ingredient of Licorice, has been used for centuries to treat many chronic diseases. ILG inhibits the MyD88-dependent pathway by inhibiting the activity of inhibitor-kappaB kinase. However, it is not known whether ILG inhibits the TRIF-dependent pathway. To evaluate the therapeutic potential of ILG, we examined its effect on signal transduction via the TRIF-dependent pathway of TLRs induced by several agonists. ILG inhibited nuclear factor-kappaB and interferon regulatory factor 3 activation induced by lipopolysaccharide or polyinosinic-polycytidylic acid. ILG inhibited the lipopolysaccharide-induced phosphorylation of interferon regulatory factor 3 as well as interferon-inducible genes such as interferon inducible protein-10, and regulated activation of normal T-cell expressed and secreted (RANTES). These results suggest that ILG can modulate TRIF-dependent signaling pathways of TLRs, leading to decreased inflammatory gene expression.
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PMID:Suppression of the TRIF-dependent signaling pathway of toll-like receptors by isoliquiritigenin in RAW264.7 macrophages. 1980 99


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