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)

The cellular origins of type I and type II interferons released into the circulation of mice with delayed hypersensitivity were investigated. We determined the effect of treatment with various immunosuppressive agents, including cyclophosphamide, cycloheximide, antithymocyte serum, and whole-body X-irradiation, on the release of interferons after intravenous injection of specific (old tuberculin) or nonspecific (lipopolysaccharide) stimuli. The results suggest that (i) a heterogeneous population of lymphocytes (T and B cells) produces type II interferon, (ii) type I interferon is produced by a different cell population, and (iii) type II interferon is produced de novo after challenge with old tuberculin of mice sensitized with Mycobacterium bovis BCG.
 ...
PMID:Cellular source of interferons in the circulation of mice with delayed hypersensitivity. 33 40

Mice with delayed hypersensitivity induced by infection with Mycobacterium bovis strain BCG were desensitized by a single large dose of specific antigen (old tuberculin, OT) or a nonspecific interferon stimulus (bacterial lipopolysaccharide, LPS). Subsequent challenge of the desensitized animals revealed only a homologous hyporeactivity, that is, mice desensitized with OT showed decreased type II and migration inhibitory factor (MIF) responses to the specific antigen, which were unaffected by desensitization with LPS. Conversely, mice desensitized with LPS showed a decreased type I interferon and MIF response to LPS, which was unaffected by desensitization with OT. These results suggest that type I interferon and its accompanying low-titered MIF activity are produced by cell populations different from those that produce type II interferon and its accompanying high-titered MIF activity.
 ...
PMID:Type I and II interferons and migration inhibitory factor: production in Mycobacterium bovis BCG-infected mice desensitized with old tuberculin or lipopolysaccharide. 34 89

Lung macrophages from uninfected CD1 mice support the replication of influenza viruses (H1N1 and H0N1), but the cells from influenza-infected mice do not. The possible mechanisms of this resistance were investigated. Murine macrophages were "activated" in vitro with lipopolysaccharide and lymphokines, and in both cases activation was associated with resistance of cells to infection with influenza virus. Exposure of alveolar macrophages in vitro to 500 U of purified type I interferon per ml enhanced cell spreading and Fc receptor-mediated phagocytosis, suggesting macrophage activation, and protected the cells against infection with influenza virus. Alveolar macrophages were also protected by a soluble factor in the bronchoalveolar washings from influenza-infected mice. This effect was not virus specific and was abolished by anti-interferon serum.
 ...
PMID:Role of macrophage activation and interferon in the resistance of alveolar macrophages from infected mice to influenza virus. 617 88

Apoptosis plays an important role in generating and maintaining an effective immune system. Many pathogens can perturb the homeostasis of the immune system by either inducing or suppressing cell death of immune cells. Using bovine macrophages as a model, we found that interferon-alpha, one of the host's responses to viral infection, can prime macrophages for activation-induced apoptosis. Exposure of bovine bone-marrow-derived macrophages to interferon-alpha and subsequent activation with lipopolysaccharide led to a strong downregulation of the macrophages' nitric oxide production when compared to lipopolysaccharide stimulation alone. We could show that this was due to induction of apoptosis after activation of the cells. Herpesvirus-induced type I interferon also primed bovine macrophages for lipopolysaccharide-induced apoptosis. Our studies describe how in a novel pathway an antiviral immune response could contribute to pathological sequelae of viral diseases.
 ...
PMID:Interferon-alpha primes macrophages for lipopolysaccharide-induced apoptosis. 748 62

Under normal physiological conditions, PTH-related protein (PTHrP) is produced in a wide variety of tissues and is thought to act locally in an autocrine or paracrine fashion more analogous to cytokines than to classic hormones such as PTH. In addition, we have recently shown that, like cytokines, PTHrP is induced in the spleen during the response to sublethal doses of endotoxin [lipopolysaccharide (LPS)] an effect that is mediated by tumor necrosis factor (TNF). As complex cytokine cascades are induced in response to infectious or inflammatory stimuli, the effects of other prototypical inflammatory [interferon-gamma (IFN gamma)] or antiinflammatory [interleukin-4 (IL-4)] cytokines on PTHrP gene expression were studied. Paradoxically, IFN gamma (50 micrograms), a cytokine that usually synergizes with TNF, inhibited LPS induction of splenic PTHrP messenger RNA (mRNA) levels in LPS-sensitive C3H/OuJ (OuJ) and LPS-resistant C3H/HeJ (HeJ) mice. The stimulation of splenic PTHrP mRNA levels caused by the administration of TNF alpha or interleukin-1 beta was similarly inhibited by IFN gamma, a type II interferon. In contrast, IFN alpha (50 micrograms), a type I interferon, stimulated splenic levels of PTHrP mRNA. IL-4, a prototypical antiinflammatory cytokine, also had a paradoxical effect on LPS induction of splenic PTHrP mRNA levels. Instead of inhibiting LPS induction of splenic PTHrP mRNA levels in OuJ or HeJ mice, IL-4 (200 ng) actually stimulated PTHrP mRNA levels. These complex cytokine interactions suggest that the expression of PTHrP in response to infectious or inflammatory stimuli depends on the counterbalancing effects of the specific cytokine networks induced by each stimulus.
 ...
PMID:Cytokine regulation of parathyroid hormone-related protein messenger ribonucleic acid levels in mouse spleen: paradoxical effects of interferon-gamma and interleukin-4. 751 68

Bovine bone marrow-derived macrophages infected with the cytopathic biotype of bovine viral diarrhea virus released an antiviral activity into the supernatant which was tentatively characterized as type I interferon because of its physicochemical properties. Such supernatants primed both infected and uninfected macrophages for decreased nitric oxide production and apoptosis in response to lipopolysaccharide. This finding strongly suggests a role of this pathway in the pathogenesis of mucosal disease, a lethal form of infection with cytopathic bovine viral diarrhea virus in which the principal lesions are located in the oral cavity and the gastrointestinal tract, which are known to contain a high concentration of endotoxin.
 ...
PMID:Macrophages infected with cytopathic bovine viral diarrhea virus release a factor(s) capable of priming uninfected macrophages for activation-induced apoptosis. 906 Jun 90

Proliferation of memory-phenotype (CD44hi) CD8+ cells induced by infectious agents can be mimicked by injection of type I interferon (IFN I) and by IFN I-inducing agents such as lipopolysaccharide and Poly I:C; such proliferation does not affect naive T cells and appears to be TCR independent. Since IFN I inhibits proliferation in vitro, IFN I-induced proliferation of CD8+ cells in vivo presumably occurs indirectly through production of secondary cytokines, e.g., interleukin-2 (IL-2) or IL-15. We show here that, unlike IL-2, IL-15 closely mimics the effects of IFN I in causing strong and selective stimulation of memory-phenotype CD44hi CD8+ (but not CD4+) cells in vivo; similar specificity applies to purified T cells in vitro and correlates with much higher expression of IL-2Rbeta on CD8+ cells than on CD4+ cells.
 ...
PMID:Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15. 962 Jun 80

Immune responses to infectious agents, especially viruses, are often associated with extensive proliferation of T cells and transient enlargement of the lymphoid tissues. Since the precursor frequency of T cells for specific antigen is low, the bulk of the T cells proliferating in the primary response are presumably stimulated via non-antigen-specific mechanisms, e.g. via cytokines elicited by the infectious agent concerned. Such 'bystander' stimulation of T cells occurs in mice injected with agents that elicit production of type I interferon (IFN I). Induction of IFN I in vivo causes marked stimulation of the CD44hi subset of CD8+ T cells and is prominent after injection of live viruses or products of bacteria such as lipopolysaccharide. Cytokines elicited by infectious agents may act as adjuvants during the primary response and could serve to boost the survival of long-lived memory cells.
 ...
PMID:Bystander stimulation of T cells in vivo by cytokines. 965 47

We have previously observed that HIV-1 replication is suppressed in uninflamed lung and increased during tuberculosis. In vitro THP-1 cell-derived macrophages inhibited HIV-1 replication after infection with Mycobacterium tuberculosis. Suppression of HIV-1 replication was associated with inhibition of the HIV-1 long terminal repeat (LTR) and induction of ISGF-3, a type I interferon (IFN)-specific transcription factor. Repression of the HIV-1 LTR required intact CCAAT/enhancer binding protein (C/EBP) sites. THP-1 cell-derived macrophages infected with M. tuberculosis, lipopolysaccharide, or IFN-beta induced the 16-kD inhibitory C/EBPbeta isoform and coincidentally repressed HIV-1 LTR transcription. C/EBPbeta was the predominant C/EBP family member produced in THP-1 macrophages during HIV-1 LTR repression. In vivo, alveolar macrophages from uninflamed lung strongly expressed inhibitory 16-kD C/EBPbeta, but pulmonary tuberculosis abolished inhibitory C/EBPbeta expression and induced a novel C/EBP DNA binding protein. Therefore, in vitro, proinflammatory stimulation produces an IFN response inhibiting viral replication by induction of a C/EBPbeta transcriptional repressor. THP-1 cell-derived macrophages stimulated with type I IFN are similar to alveolar macrophages in the uninflamed lung in vivo. In contrast, the cellular immune response in active pulmonary tuberculosis disrupts this innate immunity, switching C/EBP expression and allowing high level viral replication.
 ...
PMID:Type I interferon induces inhibitory 16-kD CCAAT/ enhancer binding protein (C/EBP)beta, repressing the HIV-1 long terminal repeat in macrophages: pulmonary tuberculosis alters C/EBP expression, enhancing HIV-1 replication. 976 5

We generated mice carrying a STAT3 allele amenable to Cre-mediated deletion and intercrossed them with Mx-Cre transgenic mice, in which the expression of Cre recombinase can be induced by type I interferon. Interferon-induced deletion of STAT3 occurred very efficiently (more than 90%) in the liver and slightly less efficiently (about 70%) in the bone marrow. Analysis of the induction of liver acute-phase genes in response to bacterial lipopolysaccharide unequivocally identifies STAT3 as a fundamental mediator of their induction. The different degrees of defectiveness displayed by the various genes allowed us to differentiate them into three separate groups according to their degree of dependence on STAT3. Induction was totally defective for group I genes, defective at 24 h but almost normal at earlier time points for group II genes, and only slightly defective for group III genes. This division was in good agreement with the known structures of the respective promoters. We also found that the overall induction of the transcription factors C/EBP beta and -delta was only minimally defective in the absence of STAT3. Finally, even though corticosterone levels and action were found to be normal in the conditional-mutant mice, production of both proinflammatory and antiinflammatory cytokines was increased and prolonged, probably as a result of STAT3 deletion in macrophages.
 ...
PMID:Essential role of STAT3 in the control of the acute-phase response as revealed by inducible gene inactivation [correction of activation] in the liver. 1123 99


1 2 3 4 5 6 7 8 Next >>