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)

We have identified and characterized a novel member of the ankyrin-repeat family named 'molecule possessing ankyrin-repeats induced by lipopolysaccharide' (MAIL). The C-terminal portion of MAIL shared high sequence homology with the I kappa B family. Intraperitoneal injection of lipopolysaccharide (LPS) into mice rapidly (<0.5 h) induced MAIL mRNA in various tissues, particularly in the spleen, lymph node, and lung. Ectopically expressed MAIL was localized in the nucleus, and remarkably potentiated the LPS-induced mRNA expression and secretion of interleukin (IL)-6 in Swiss 3T3 cells. These findings indicate that MAIL is one of the nuclear I kappa B proteins and an activator of IL-6 production.
 ...
PMID:MAIL, a novel nuclear I kappa B protein that potentiates LPS-induced IL-6 production. 1108 64

The transcription factor nuclear factor-kappaB (NF-kappaB) plays crucial roles in a wide variety of cellular functions and its activity is strictly regulated by cytosolic inhibitors known as IkappaBs. We here report a new member of the IkappaB protein family, IkappaB-zeta, harboring six ankyrin repeats at its carboxyl terminus. IkappaB-zeta mRNA is strongly induced after stimulation by lipopolysaccharide. The induction of IkappaB-zeta is also observed by stimulation with interleukin-1beta but not by tumor necrosis factor-alpha. In contrast to cytosolic IkappaB-alpha, -beta, and -epsilon, the induced IkappaB-zeta localizes in the nucleus via its amino-terminal region, which shows no homology with other proteins. Transiently expressed IkappaB-zeta inhibits the NF-kappaB activity without affecting the nuclear translocation of NF-kappaB upon stimulation. The expressed IkappaB-zeta preferentially associates with the NF-kappaB subunit p50 rather than p65 and recombinant IkappaB-zeta proteins inhibit the DNA binding of the p65/p50 heterodimer and the p50/p50 homodimer. Thus, IkappaB-zeta negatively regulates NF-kappaB activity in the nucleus, possibly in order to prevent excessive inflammation. Moreover, transfection of IkappaB-zeta renders cells more susceptible to apoptosis induced by tumor necrosis factor-alpha. The proapoptotic activity of IkappaB-zeta further suggests that it might be one of key regulators for inflammation and other biologically relevant processes.
 ...
PMID:A novel IkappaB protein, IkappaB-zeta, induced by proinflammatory stimuli, negatively regulates nuclear factor-kappaB in the nuclei. 1135 51

The Mail (molecule possessing ankyrin repeats induced by lipopolysaccharide) protein is a member of the IkappaB family. It has six ankyrin repeats that are conserved in other IkappaB proteins, such as IkappaB-alpha and Bcl-3. Mail mRNA expression is induced rapidly following lipopolysaccharide (LPS) injection, most notably in the spleen, lung, and lymph nodes of mice, where immune cells, such as lymphocytes and macrophages, are abundant. In this study, we cloned and characterized the Mail gene. The isolated genomic clones span approximately 30 kb and encompass the entire gene. Comparisons with Mail cDNA revealed that the Mail gene consists of 14 exons. Several splice junctions encoding ankyrin repeats are conserved among Mail and other IkappaB family genes. Southern hybridization showed that Mail is a single-copy gene. Using fluorescence in situ hybridization analysis, mouse and rat Mail genes were mapped to Chromosome (Chr) 16C1.2-C1.3 and Chr 11q21.1, respectively. Primer extension determined the transcription start site of Mail. Sequence analysis of the proximal promoter region revealed the presence of a TATA box and putative transcription factor-binding sites, such as those for NF-kappaB and NF-IL6. This region is sufficient to drive high-level reporter gene expression in LPS-stimulated transfected cells.
 ...
PMID:Genomic organization, chromosomal localization, and promoter analysis of the mouse Mail gene. 1179 98

Molecule possessing ankyrin-repeats induced by lipopolysaccharide (MAIL) is a nuclear IkappaB protein recently identified as a molecule appearing in immunocompetent organs after administration of bacterial lipopolysaccharide (LPS). Participation of Toll-like receptor (TLR) 4, which is a major form of LPS receptors, in the LPS-induced MAIL expression was investigated. When a human myelomonocytic cell line U937 was treated with phorbol 12-myristate 13-acetate for 3 days, the LPS-induced MAIL expression was much potentiated in parallel with an increase in TLR4 expression. The MAIL induction was attenuated when the cells were treated with a neutralizing antibody against TLR4. The in vivo induction of MAIL in the spleen was smaller in mice having a missense mutation of the Tlr4 gene than in normal control mice. These results collectively indicate that TLR4 contributes, at least in part, MAIL induction after LPS stimulation.
 ...
PMID:Bacterial lipopolysaccharide induces mRNA expression of an IkappaB MAIL through toll-like receptor 4. 1206 74

Molecule possessing ankyrin-repeats induced by lipopolysaccharide (MAIL), a recently cloned nuclear IkappaB protein induced by lipopolysaccharide (LPS) stimulation in lymphoid organs, is involved in the regulation of inflammatory responses. The present in situ hybridization and immunohistochemical analyses revealed the distinct expression of the MAIL mRNA and protein in B-lymphocytes of the white pulp of the spleen and cortical lymphoid follicles of lymph nodes in LPS-injected mice. MAIL signals were also localized in F4/80-positive macrophages in these organs. LPS clearly induced MAIL expression in cultured B-lymphocytes and monocytes/macrophages, but only faintly so in T-lymphocytes, fibroblasts, and endothelial cells. MAIL was also induced by inflammatory cytokines such as interleukin-1 and -6, and tumor necrosis factor in cultured cells. Northern blot, Western blot, and in situ hybridization analyses showed that the major expression product of the Mail gene was a long splicing variant (MAIL-L) rather than a short one, both in lymphoid organs and cultured cells. These results collectively indicate that LPS induces MAIL-L predominantly in B-lymphocytes and macrophages.
 ...
PMID:Bacterial lipopolysaccharide-induced expression of the IkappaB protein MAIL in B-lymphocytes and macrophages. 1270 54

Activation of nuclear factor-kappaB (NF-kappaB), a prominent cellular response to bacterial endotoxin or other microbial products, must be strictly regulated because excessive activation leads to overproduction of cytotoxic cytokines that culminates in septic shock. During screening for genes up-regulated upon inflammation, we identified a new member of the IkappaB family proteins with the ankyrin-repeats. This protein, designated IkappaB-zeta, is hardly detectable in resting cells, but is strongly induced upon stimulation by lipopolysaccharide, which stimulates cells through the Toll-like receptor 4. Interleukin-1beta stimulation also results in the strong induction of IkappaB-zeta, but tumor necrosis factor-alpha does not. In contrast to IkappaB-alpha or IkappaB-beta, IkappaB-zeta localizes in the nucleus, where it inhibits NF-kappaB activity. NF-kappaB activity is essential for the induction of IkappaB-zeta, but is not sufficient. Thus, this protein is a new anti-inflammatory protein, which is specifically induced upon inflammation to regulate NF-kappaB activity.
 ...
PMID:IkappaB-zeta, a new anti-inflammatory nuclear protein induced by lipopolysaccharide, is a negative regulator for nuclear factor-kappaB. 1283 61

Molecule possessing ankyrin-repeats induced by lipopolysaccharide (MAIL) is known as an IkappaB protein induced after administration of bacterial lipopolysaccharide (LPS) to mice. In the present study, we cloned bovine MAIL cDNA and examined its mRNA expression in white blood cells isolated from Holstein cows. Bovine MAIL had more than 80% amino acid identities with murine and human MAILs, highly conserved ankyrin-repeat motifs and PEST-like sequences. Bovine MAIL mRNA was undetectable in isolated peripheral white blood cells, but rapidly induced (<1h) after stimulation by LPS and lipid A in vitro in a dose-dependent manner. The lipid A-induced MAIL mRNA expression was found in polymorphonuclear cells, monocytes/macrophages and total lymphocytes, but not in T-lymphocytes. MAIL mRNA was also induced in vivo in peripheral blood leukocytes of cows after intramammary injection of Escherichia coli derived from coliform mastitis. Thus, bovine MAIL, as rodent MAILs, is induced by inflammatory stimuli in specific immune cells in vitro and in vivo, suggesting a role in inflammatory responses to bacterial infection in cattle.
 ...
PMID:Cloning of bovine MAIL and its mRNA expression in white blood cells of Holstein cows. 1501 Feb 26

The complete sequence of the 1,267,782 bp genome of Wolbachia pipientis wMel, an obligate intracellular bacteria of Drosophila melanogaster, has been determined. Wolbachia, which are found in a variety of invertebrate species, are of great interest due to their diverse interactions with different hosts, which range from many forms of reproductive parasitism to mutualistic symbioses. Analysis of the wMel genome, in particular phylogenomic comparisons with other intracellular bacteria, has revealed many insights into the biology and evolution of wMel and Wolbachia in general. For example, the wMel genome is unique among sequenced obligate intracellular species in both being highly streamlined and containing very high levels of repetitive DNA and mobile DNA elements. This observation, coupled with multiple evolutionary reconstructions, suggests that natural selection is somewhat inefficient in wMel, most likely owing to the occurrence of repeated population bottlenecks. Genome analysis predicts many metabolic differences with the closely related Rickettsia species, including the presence of intact glycolysis and purine synthesis, which may compensate for an inability to obtain ATP directly from its host, as Rickettsia can. Other discoveries include the apparent inability of wMel to synthesize lipopolysaccharide and the presence of the most genes encoding proteins with ankyrin repeat domains of any prokaryotic genome yet sequenced. Despite the ability of wMel to infect the germline of its host, we find no evidence for either recent lateral gene transfer between wMel and D. melanogaster or older transfers between Wolbachia and any host. Evolutionary analysis further supports the hypothesis that mitochondria share a common ancestor with the alpha-Proteobacteria, but shows little support for the grouping of mitochondria with species in the order Rickettsiales. With the availability of the complete genomes of both species and excellent genetic tools for the host, the wMel-D. melanogaster symbiosis is now an ideal system for studying the biology and evolution of Wolbachia infections.
 ...
PMID:Phylogenomics of the reproductive parasite Wolbachia pipientis wMel: a streamlined genome overrun by mobile genetic elements. 1502 19

Toll-like receptors (TLRs) recognize microbial components and trigger the inflammatory and immune responses against pathogens. IkappaBzeta (also known as MAIL and INAP) is an ankyrin-repeat-containing nuclear protein that is highly homologous to the IkappaB family member Bcl-3 (refs 1-6). Transcription of IkappaBzeta is rapidly induced by stimulation with TLR ligands and interleukin-1 (IL-1). Here we show that IkappaBzeta is indispensable for the expression of a subset of genes activated in TLR/IL-1R signalling pathways. IkappaBzeta-deficient cells show severe impairment of IL-6 production in response to a variety of TLR ligands as well as IL-1, but not in response to tumour-necrosis factor-alpha. Endogenous IkappaBzeta specifically associates with the p50 subunit of NF-kappaB, and is recruited to the NF-kappaB binding site of the IL-6 promoter on stimulation. Moreover, NF-kappaB1/p50-deficient mice show responses to TLR/IL-1R ligands similar to those of IkappaBzeta-deficient mice. Endotoxin-induced expression of other genes such as Il12b and Csf2 is also abrogated in IkappaBzeta-deficient macrophages. Given that the lipopolysaccharide-induced transcription of IkappaBzeta occurs earlier than transcription of these genes, some TLR/IL-1R-mediated responses may be regulated in a gene expression process of at least two steps that requires inducible IkappaBzeta.
 ...
PMID:Regulation of Toll/IL-1-receptor-mediated gene expression by the inducible nuclear protein IkappaBzeta. 1524 16

MAIL (molecule-possessing ankyrin repeats induced by lipopolysaccharide) is a nuclear IkappaB protein that is also termed interleukin-1-inducible nuclear ankyrin repeat protein or inhibitor of nuclear factor kappaB (IkappaB) zeta. In this study, we generated Mail-/- mice to investigate the roles of MAIL in whole organisms. Mail-/- mice grew normally until 4-8 weeks after birth, when they began to develop lesions in the skin of the periocular region, face, and neck. MAIL mRNA and protein were constitutively expressed in the skin of wild type controls, especially in the keratinocytes. Serum IgE was higher in Mail-/- mice than in normal. Histopathological analysis indicated that the Mail-/- skin lesions appeared to be atopic dermatitis (AD) eczema with inflammatory cell infiltration. In addition, markedly elevated expression of some chemokines such as thymus and activation-regulated chemokine was detected in the Mail-/- skin lesions, similar to that observed in the skin of patients with AD. In Mail-/- mice, MAIL-deficient keratinocytes might be activated to produce chemokines and induce intraepidermal filtration of inflammatory cells, resulting in the onset of the AD-like disease. These findings suggest that MAIL is an essential molecule for homeostatic regulation of skin immunity. The Mail-/- mouse is a valuable new animal model for research on AD.
 ...
PMID:Targeted disruption of MAIL, a nuclear IkappaB protein, leads to severe atopic dermatitis-like disease. 1549 98


1 2 3 Next >>