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)

The progression of peripheral arterial disease (PAD) is poorly understood but may be caused by an underlying inflammatory dysfunction. This study therefore profiled interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, anticardiolipin, and anti-beta2-glycoprotein 1 antibody concentrations and characterized patients' inflammatory response in vitro. Patients were classified according to World Health Organization criteria and ankle-brachial pressure index into critical ischemics (n=20), stable claudicants (n=20), and controls (n=20). In vitro studies involved culturing whole blood with RPMI-1640 for 24hr with and without 1 microg/mL lipopolysaccharide and profiling cytokine production. Autoantibody levels were measured using enzyme-linked immunosorbent assays, while cytokine profiles were determined by multiplex immunoassay. Serum IL-6, IL-10, IL-13, and anti-beta2-glycoprotein 1 antibody levels were higher in PAD (p<0.05). In the case of IL-6 and anti-beta2-glycoprotein 1 antibody, levels reflected increasing disease severity (p<0.05). In vitro studies revealed that IL-8 and IL-13 secretory capacities were significantly higher in PAD after 6 hr. However, when these were standardized against patient leukocyte count, cytokine production profiles did not differ. PAD features an increased inflammatory burden irrespective of Th1:Th2 cytokine type; this is more pronounced with increasing disease severity. However, the inflammatory hyperresponsiveness of cultured whole blood from PAD patients probably relates to associated leukocytosis, rather than being attributable to an inherent inflammatory dysfunction.
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PMID:Inflammatory profiling of peripheral arterial disease. 1865 86

Patients with chronic mucocutaneous candidiasis (CMC) suffer persistent infections with the yeast Candida. CMC includes patients with autoimmune regulator (AIRE) gene mutations who have autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), and patients without known mutations. CMC patients have dysregulated cytokine production, and dendritic cells (DCs), as central orchestrators, may underlie pathogenic disease mechanisms. In 29 patients with CMC (13 with APECED) and controls, we generated monocyte-derived DCs, stimulated them with Candida albicans, Toll-like receptor-2/6 ligand and lipopolysaccharide to assess cytokine production [interleukin (IL)-12p70, IL-23, interferon (IFN)-gamma, IL-2, tumour necrosis factor (TNF)-alpha, IL-6, transforming growth factor-beta, IL-10, IL-5, IL-13] and cell-surface maturation marker expression (CD83, CD86, human leucocyte antigen D-related). In both APECED and non-APECED CMC patients, we demonstrate impairment of DC function as evidenced by altered cytokine expression profiles and DC maturation/activation: (1) both groups over-produce IL-2, IFN-gamma, TNF-alpha and IL-13 and demonstrate impaired DC maturation. (2) Only non-APECED patients showed markedly decreased Candida-stimulated production of IL-23 and markedly increased production of IL-6, suggesting impairment of the IL-6/IL-23/T helper type 17 axis. (3) In contrast, only APECED patients showed DC hyperactivation, which may underlie altered T cell responsiveness, autoimmunity and impaired response to Candida. We demonstrate different pathogenic mechanisms on the same immune response pathway underlying increased susceptibility to Candida infection in these patients.
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PMID:Impaired dendritic cell maturation and cytokine production in patients with chronic mucocutanous candidiasis with or without APECED. 1903 23

There is increasing evidence for involvement of the immune system in functional gastrointestinal disorder (FGID), including onset after acute gastrointestinal infections, genotypes resulting in altered cytokine expression and abnormal presence of immune cells. Our aim was to assess cellular and humoral immune responses in (i) FGIDs, compared to healthy subjects and (ii) acute vs unspecified onset FGIDs. Lymphocytic [interleukin (IL)-5, IL-10, IL-13 and interferon gamma (IFN-gamma)] and monocytic [IL-10, IL-12, tumour necrosis factor (TNF)-alpha] cytokine production was characterized at baseline and after stimulation with phytohemagglutinine and anti-CD28 or lipopolysaccharide (LPS) in controls (n = 32), irritable bowel syndrome (IBS) (n = 30), functional dyspepsia (FD) (n = 23) and non-cardiac chest pain (NCCP) (n = 15). Serum IL-6 and IL-10 concentrations were compared, and the immunophenotype was assessed using fluorescent-activated cell sorter. Findings were compared for acute vs unspecified onset FGID. Compared to controls, stimulated lymphocyte expression of IL-5 and IL-13 was enhanced in IBS, FD and NCCP (all P < 0.05). Conversely, the stimulated monocytic IL-12 and lymphocytic IL-10 expression were reduced in IBS and FD, while IFN-gamma expression was also reduced in FD patients. Except for an increase in the numbers of CD3(+)CD45RA(+)CD45RO(+) cells, no distinct cellular profile was detected. Patients with a presumed acute onset of their symptoms had higher serum IL-10 levels and more CD3(+)CD45RA(+)CD45RO(+) cells, while TNF-alpha levels following stimulation with LPS were higher in FD patients reporting an acute onset. A shift towards a Th2 cytokine profile is present in FGID, while the cellular immunophenotype remains largely unchanged. Further research is indicated and could provide new therapeutic strategies for these disorders.
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PMID:Immune dysfunction in patients with functional gastrointestinal disorders. 1912 84

Staphylococcal scalded-skin syndrome (SSSS) is an exfoliative dermatitis resultant from the infection with exfoliative-toxin-producing (ET) Staphylococcus aureus. This syndrome usually occurs in children, while adult cases are generally linked to renal-deficiency or immunossupresion. A case of a 74 year old woman presenting SSSS after hospital admission due to cardiovascular disorders is presented and discussed. Cytokines (TNF-alpha, IFN-gamma, IL-6, IL-13 and IL-10) and nitric oxide (NO) production in vitro by whole blood leukocytes (WBL) were investigated. Leukocytes stimulated by lipopolysaccharide or phytohemagglutinin produced increased IFN-gamma, TNF-alpha, IL-13 and NO levels after treatment. Based on these results, immunological aspects of the disease are discussed.
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PMID:Cytokine and nitric oxide production in an adult patient with staphylococcal scalded skin syndrome. 1924 72

Macrophages are involved in both innate and adaptative immune responses. Depending on the types of cytokines that macrophages are exposed to, these cells are subjected to classical (Th1) or alternative (Th2) activation. In the first case, macrophages, particularly when activated by interferon gamma (IFN-alpha) or by lipopolysaccharide (LPS), have the capacity, through the production of NO and other intermediates, to destroy the remaining microorganisms in the inflammatory loci. In the second case, after exposure to cytokines such as IL-4, IL-10, or IL-13, macrophages produce polyamines and proline, which induce proliferation and collagen production, respectively. Interestingly, in both classical and alternative activation, the essential substrate that drives these pathways is the amino acid arginine. NO synthase 2 (NOS2) is induced by IFN-alpha or LPS and degrades arginine into OH-arginine and then into NO. Arginase is induced by Th2-type cytokines, which convert arginine into ornithine and subsequently into polyamines and proline. In this chapter, we present simple and direct methods for analyzing the properties of macrophage populations to determine whether they exhibit either a classical or alternatively activated phenotype.
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PMID:Macrophage activation: classical versus alternative. 1934 9

Diversity in macrophage responsiveness to inflammatory stimuli has resulted in the description of a new paradigm wherein macrophages are referred to as polarized into one of two distinct phenotypes, classically activated (M1) macrophages and alternatively activated (M2) macrophages. Classically activated, M1 or "killer" macrophages are thought to play a critical role in destroying foreign organisms and tumor cells, while alternatively activated M2 or "healer" macrophages are thought to be important in debris scavenging, wound healing, and angiogenesis. M2 macrophages may also play key roles in chronic infections, tumorigenesis, and tumor metastasis. It is therefore important to establish models of M1 and M2 polarized macrophages to study their characteristics and amenability to manipulation. M1 macrophages are typically derived from myeloid progenitors with murine macrophage-colony-stimulating factor (M-CSF, also known as CSF-1), while M2 macrophages are thought to be derived from mature M1 macrophages by treatment with interleukin-4 (IL-4) or IL-13. M2 macrophages can also be isolated from SH2-containing inositol 5'-phosphatase (SHIP)-/- mice by harvesting macrophages from peritoneal lavage fluids or they can be derived from SHIP-/- bone marrow aspirate cells with addition of 5% human serum. Upon stimulation with lipopolysaccharide (LPS), M1 macrophages produce high levels of proinflammatory cytokines, low levels of anti-inflammatory cytokines, and high levels of inducible nitric oxide synthase (iNOS), which leads to nitric oxide (NO) production. M2 macrophages, on the other hand, express high levels of M2 markers Ym1 and arginase I (ArgI) and, upon stimulation with LPS, produce relatively lower levels of proinflammatory cytokines and NO and higher levels of anti-inflammatory cytokines. In this chapter, we describe methods used in our laboratory to generate and characterize alternatively activated (M2) macrophages.
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PMID:Derivation and characterization of murine alternatively activated (M2) macrophages. 1934 18

We observed previously that lipopolysaccharide (LPS) 18 h after i.p. injection of guinea pigs increased transepithelial potential difference (V(t)), hyperpolarization responses to methacholine, and hyperosmolarity-induced, epithelium-derived relaxing factor (EpDRF)-mediated relaxation responses, in excised and perfused tracheal segments. To investigate their roles in these changes, the effects of cytokines on in vitro epithelial bioelectric and smooth muscle mechanical responses were investigated using the isolated, perfused trachea preparation. Tracheas were incubated (6 h) with LPS or IL-1beta, IL-4, IL-13, IFN-gamma, TNF-alpha, singly or in combination. Incubation with LPS and cytomix (IL-1beta+IFN-gamma+TNF-alpha together) had no effect on muscle reactivity to methacholine, but potentiated D-mannitol-induced relaxation. Individually, IL-1beta and IFN-gamma inhibited methacholine-induced contractions and potentiated D-mannitol-induced relaxation responses. TNF-alpha increased contractions to methacholine but had no effect on relaxation responses to D-mannitol. Methacholine elicited hyperpolarization in low concentrations and depolarization in high concentrations. The individual cytokines decreased the hyperpolarization response to low methacholine concentrations and increased the depolarization response to high methacholine concentrations but had no effect on V(t) responses to D-mannitol. Cytomix did not affect V(t) responses to methacholine, but potentiated both the hyperpolarization and depolarization responses to D-mannitol. In Ussing chambers all agents except IL-1beta and IFN-gamma increased V(t); IL-1beta decreased slightly but none of the other agents affected transepithelial resistance (R(t)). The results indicate that cytokines and LPS alter smooth muscle reactivity to methacholine, potentiate EpDRF-mediated relaxation responses and, thereby, mimic the effects of LPS treatment in vivo, but do not recapitulate LPS' effects on V(t) responses.
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PMID:Effects of cytokines on mechanical and epithelial bioelectric responses to methacholine and hyperosmolarity in guinea-pig airways: an in vitro study. 1938 94

Alzheimer's disease (AD) brains are characterized by accumulation of amyloid beta protein (Abeta) and neuroinflammation. Increased blood-to-brain influx and decreased brain-to-blood efflux across the blood-brain barrier (BBB) have been proposed as mechanisms for Abeta accumulation. Epidemiological studies suggest that the nonsteroidal anti-inflammatory drug (NSAID) indomethacin slows the progression of AD. We hypothesized that inflammation alters BBB handling of Abeta. Mice treated with lipopolysaccharide (LPS) had increased brain influx and decreased brain efflux of Abeta, recapitulating the findings in AD. Neither influx nor efflux was mediated by LPS acting directly on BBB cells. Increased influx was mediated by a blood-borne factor, indomethacin-independent, blocked by the triglyceride triolein, and not related to expression of the blood-to-brain transporter of Abeta, RAGE. Serum levels of IL-6, IL-10, IL-13, and MCP-1 mirrored changes in Abeta influx. Decreased efflux was blocked by indomethacin and accompanied by decreased protein expression of the brain-to-blood transporter of Abeta, LRP-1. LPS paradoxically increased expression of neuronal LRP-1, a major source of Abeta. Thus, inflammation potentially increases brain levels of Abeta by three mechanisms: increased influx, decreased efflux, and increased neuronal production.
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PMID:Lipopolysaccharide alters the blood-brain barrier transport of amyloid beta protein: a mechanism for inflammation in the progression of Alzheimer's disease. 1948 46

Pig farmers and cigarette smokers are continuously exposed to pathogen-associated molecular patterns (PAMPs) have an increased prevalence of respiratory disorders, such as chronic bronchitis and chronic obstructive pulmonary decease (COPD). We hypothesized that markers of innate immunity, T-helper (Th) cell cytokine profile and acute responses to pro-inflammatory stimuli differ between smokers and farmers, who are exposed to organic material on a daily basis and healthy non-exposed subjects. Eleven non-smoking pig farmers, 12 non-farming smokers and 12 controls underwent bronchial lipopolysaccharide (LPS) challenge and exposure in a pig barn during 3 h on separate days. Toll-like receptor 2 (TLR2), TLR4 and CD14 on blood monocytes and neutrophils and intracellular cytokine profile of Th cells were assessed before and 7 h after exposures. The same outcomes were analysed on peripheral blood and purified neutrophils from farmers and controls after stimulation ex vivo with dust from a pig barn and LPS. Circulating neutrophils and IL-13 and IL-4 producing Th cells were increased in smokers and farmers and TLR2 expression on blood monocytes was decreased in farmers compared with controls and smokers. After in vivo exposure, altered TLR expression was only observed in controls and the ex vivo stimulations showed an attenuated response in farmers compared to the control group. The inflammatory systemic response to pro-inflammatory stimuli is altered in farmers and smokers probably because of adaptive mechanisms arising from chronic exposure to organic material. This increased proportion of Th2 cells and reduced TLR2 expression may have health-related implications and may be related to the increased prevalence of respiratory disorders observed in these groups.
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PMID:Altered innate immune response in farmers and smokers. 1967 20

The diarylheptanoid, oregonin (ORE), which was isolated from the bark of Alnus japonica Steudel that grows natively in Korea, has been known to exert antioxidative, anti-inflammatory, anti-cancer and immune response inhibitory effects. The antioxidative effect of ORE was observed on the superoxide and 1,1-diphenyl-2-picrylhydrazyl radical, as well as on the expression of inducible nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-treated RAW264.7 macrophages. The statistically significant inhibitory action of ORE against production of cytokines induced by bacterial products or by interleukin (IL)-1beta, free radicals and nitrogen species, and a corresponding increase in cellular calcium concentration because of ORE were confirmed in bone marrow and spleen dendritic cells that are known to play important functions in the development and advancement of atopic dermatitis (AD). It was thus expected that ORE would exert a beneficial effect in the treatment of AD. A study on the pharmaceutical benefits of ORE against AD has not yet been conducted in vivo. We therefore used an in vivo AD animal model, namely the NC/Nga mice, and by applying ORE onto the animals through skin application as well as intraperitoneal injection, we attempted to evaluate the benefits of ORE in this system. Evaluation of ORE was conducted by following the SCORE method to score the effect, as well as by measuring the Th2 cytokines IL-4, IL-5 and IL-13 levels from serum and lymphocytes, and IgE and eosinophil levels from serum. Additionally, the expression of mRNA and protein levels was estimated using real-time polymerase chain reaction and Western blotting analysis. The following categories of clinical evaluation, Th2 cytokines IL-4, IL-5 and IL-13 values, serum IgE levels, serum eosinophil levels, and mRNA and protein expression levels of iNOS and COX-2, were evaluated from topical application and intraperitoneal injection groups of ORE. The effects of ORE on AD in NC/Nga mice were confirmed as being similar to the positive control group, while a significant difference with the negative control group was observed. The results presented in this report suggest that ORE might be beneficial in the treatment of AD.
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PMID:Effect of topical application and intraperitoneal injection of oregonin on atopic dermatitis in NC/Nga mice. 1984 16


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