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)

Actinobacillus pleuropneumoniae produces several hemolysins/cytotoxins that may be important in the pathogenesis of acute lesions. Little is known, however, about the role of these virulence factors in chronic disease or the carrier state. We investigated the effects of live bacterial infection and transthoracic injection of a sterile culture supernatant on primary lymphoid organs and lymphocyte populations. Transthoracic inoculation of mice or intranasal inoculation of pigs with virulent A. pleuropneumoniae serotypes 1 and 7 induced thymic cortical lymphoid necrosis. These lesions were reproduced in mice by transthoracic injection of a concentrated sterile culture supernatant. The cytotoxic effect of this culture supernatant was also demonstrated in vitro by using a tetrazolium dye reduction assay. Both porcine and murine thymic lymphocytes as well as splenic T lymphocytes were susceptible to the toxin. Porcine convalescent serum, but not preimmune serum, prevented thymic lesions and neutralized the in vitro cytotoxic effect of the culture supernatant on murine thymic lymphocytes. Thymic lesions also were reproduced in mice by using purified lipopolysaccharide (LPS) from Escherichia coli O111:B4; however, LPS had no in vitro cytotoxic effect on either porcine or murine thymic lymphocytes. These results suggest that secreted A. pleuropneumoniae toxin(s) is capable of affecting host T-lymphocyte populations and may affect host immune function.
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PMID:Actinobacillus pleuropneumoniae-induced thymic lesions in mice and pigs. 187 15

The underlying mechanisms at the organismic, cellular and molecular levels that account for rickettsial pathogenesis are beginning to be revealed. In the case of Coxiella burnetii infection, relatively recent genetic and biochemical data, as well as drug susceptibility studies, indicate a correlation between isolate type and clinical disease--chronic or short-term acute. The use of cultured cells as model host systems has revealed that, indeed, different isolates from the major classified strains of C. burnetii cause different host cell responses. Use of this and other models (guinea pigs, mice) have revealed other characteristics and properties of the rickettsiae and the infected hosts and host cells that may account, in part, for acute disease and persistent infection culminating in chronic disease. The virulence factors involved apparently include the agent's surface lipopolysaccharide; other unidentified factors have not been excluded. Molecular cloning will play a major role in elucidating the roles of these factors and in identifying other virulence determinants.
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PMID:Pathogenesis of rickettsial infections emphasis on Q fever. 188 73

Macrophage secretory products are suspected to participate in the severe lean tissue wasting related to chronic illness. The protein metabolic effects of chronic, 7-day cachectin/tumor necrosis factor (cachectin) or interleukin 1 alpha (IL-1 alpha) administration in vivo were studied in male Wistar rats that were 1) freely fed, 2) pair fed, 3) total protein and calorie starved, 4) twice daily lipopolysaccharide (LPS) administered, 5) twice daily cachectin administered, and 6) twice daily IL-1 alpha administered. LPS, cachectin, or IL-1 alpha administration produced anorexia; weight loss in these groups was comparable to respective pair-fed animals. However, LPS, cachectin, or IL-1 alpha accelerated peripheral protein wasting while preserving liver protein content, unlike the pattern in the pair-fed or starved animals in which loss of liver proteins and relative preservation of skeletal muscle protein were observed. The decrease in skeletal muscle protein content in LPS- or cytokine-treated animals was associated with coordinate decreases in muscle mRNA levels for the myofibrillar proteins myosin heavy chain, myosin light chain, actin, and in the 18S and 28S subunits of ribosomal RNA. We conclude that chronic exposure to the cytokines, IL-1 alpha or cachectin, can simulate those body and muscle protein changes seen in experimental LPS administration or chronic disease and markedly differ from the pattern of protein redistribution due to caloric restriction.
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PMID:Cachectin/TNF or IL-1 alpha induces cachexia with redistribution of body proteins. 278 90

Porphyromonas gingivalis is a gram-negative bacterium that is associated with periodontitis. It has been hypothesized that destruction of bone and periodontal connective tissue is associated with colonization of the subgingival crevicular space by P. gingivalis, although how these bacteria overcome innate host defenses is largely unknown. To examine the early cellular and molecular events of P. gingivalis interaction with host tissues, we compared lipopolysaccharide (LPS) isolated from this bacterium with Escherichia coli LPS, a potent inflammatory mediator, in a mouse model of acute inflammation. In these studies, mice were given intramuscular injections of either P. gingivalis LPS or E. coli LPS and then sacrificed after 4 h. Reverse transcriptase-PCR analysis showed that expression of mRNAs for E- and P-selectins was higher in E. coli LPS-injected muscles than in P. gingivalis LPS-injected or control phosphate-buffered-saline-injected muscles. Similarly, monocyte chemotactic protein 1 and fibroblast-induced cytokine mRNAs were expressed in E. coli LPS-injected muscles whereas their expression was reduced or absent in P. gingivalis LPS-injected samples. These results were confirmed by in situ hybridization whereby stronger hybridization for selectin mRNAs was observed in the endothelium of capillaries from E. coli LPS-injected samples than in that from P. gingivalis LPS-injected muscles. In addition, many monocytes expressing monocyte chemotactic protein 1 mRNA and polymorphonuclear leukocytes expressing fibroblast-induced cytokine mRNA were observed in E. coli LPS-injected muscles whereas only a few cells were identified in P. gingivalis LPS-injected muscles. These results demonstrate that compared with E. coli, P. gingivalis has a low biologically reactive LPS as measured by its weak activation of inflammation. This may allow P. gingivalis to evade innate host defense mechanisms, resulting in colonization and chronic disease.
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PMID:Porphyromonas gingivalis lipopolysaccharide is poorly recognized by molecular components of innate host defense in a mouse model of early inflammation. 759 Nov 24

Chlamydia pneumoniae, a Gram-negative bacterium, formerly named TWAR but identified as a distinct species since 1988, is now considered to be the most common agent of chlamydial infection in Scandinavia. C pneumoniae has a different tissue trophism from that of Chlamydia trachomatis, since C pneumoniae may infect bronchi and lungs, macrophages, monocytes, and endothelial cells. C pneumoniae, like other chlamydiae, has a slow, intracellular life cycle. An absence of reaction from the host cells, combined with scant tissual reaction owing to the low endotoxic activity of chlamydial lipopolysaccharide, may help to explain the usually discreet clinical picture. Atherosclerosis and coronary heart disease may follow chronic lung infection, and acute pneumonic episodes can trigger myocardial infarct. Asymptomatic infection with C pneumoniae is widespread. Intriguing diagnostic questions are the possible existence of a non-pathogenic carrier state, and the conceivable sensitization of the host with respect to a heterotypic, secondary chlamydial infection by, for example, C trachomatis, giving rise to an aggravated clinical picture. Early antibiotics are indicated to avoid the development of chronic disease.
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PMID:[Chlamydia pneumoniae--pathogenesis and perspectives]. 848 Feb 96

Mycoplasma arthritidis is an arthritogenic organism for rodents, producing a superantigen (MAS). It has been postulated that mycoplasmas or superantigens thereof might play a role in human rheumatoid arthritis. Since M. arthritidis fulfills both, the present study was performed to investigate MAS-specific cytokine induction. Human or murine leukocytes were stimulated with MAS, staphylococcal enterotoxin E (SEE), or lipopolysaccharide (LPS). Cytokines were measured by ELISA, Bioassay, and RT-PCR. The response to MAS in humans was individually restricted, in contrast to the response to SEE or LPS. Furthermore, MAS showed the same capacity for inducing proinflammatory cytokines as interleukin (IL)-1 IL-6, and IL-8 as SEE and LPS. However, MAS showed a significantly decreased capacity to induce the anti-inflammatory cytokine IL-10 and IL-1RA. In mice, the reactivity to MAS was strictly MHC-II restricted, in contrast to that of SEE or LPS. The individual response to MAS in humans might be explained by the difference of the HLA-DR haplotype because H-2-differing mouse strains showed the same discrepancies. MAS induced an overproduction of proinflammatory cytokines, when its ability to induce proinflammatory and anti-inflammatory cytokines was compared with those of SEE and LPS. The individual response may explain an MHC linkage, and the failure to induce anti-inflammatory cytokines may be the reason for a chronic disease in contrast to acute inflammation.
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PMID:Induction of a proinflammatory cytokine network by Mycoplasma arthritidis-derived superantigen (MAS). 891 Jul 72

1. This study investigates whether previously documented effects of interleukin-4 in down-regulating pro-inflammatory cytokine production by peripheral blood mononuclear cells (PBMCs) from healthy individuals would be reproducible in PBMCs isolated from patients with multiple organ failure (acute disease model) and gastrointestinal cancer (chronic disease model). The effects of interleukin-4 on the ability of PBMC supernatants to elicit an acute phase protein response from isolated human hepatocytes were also studied. 2. Incubation of PBMCs with interleukin-4 significantly reduced both spontaneous and lipopolysaccharide-induced production of tumour necrosis factor and lipopolysaccharide-induced interleukin-6 production, demonstrating that the PBMCs from patients with acute and chronic disease are not refractory to the effects of interleukin-4. The effects of interleukin-4 on the ability of PBMCs from the groups studied to elicit an acute phase response were complex and varied both between patient groups and individual acute phase proteins. Overall, interleukin-4 reduced the potential of PBMCs to stimulate production of the positive acute phase proteins C-reactive protein, alpha1-antichymotrypsin and alpha1-acid glycoprotein.3. This work emphasizes the pleiotropic nature of cytokines and the complex regulatory mechanisms which exist. The study illustrates the difficulties in devising in vivo intervention strategies using cytokines such as interleukin-4.
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PMID:Effect of interleukin-4 on pro-inflammatory cytokine production and the acute phase response in healthy individuals and in patients with cancer or multiple organ failure. 973 Aug 55

C57/B6 mice received intraperitoneal horse spleen apoferritin (4 mg) with lipopolysaccharide (0.05 mg); control mice received 0.15 M NaCl. Control and treated animals were killed weekly for 6 wk; blood and urine specimens were obtained, and tissue samples were secured. Treated animals showed evidence of significant chronic disease, with proteinuria, hematuria, and uremia. A mild glomerulonephritis was present at 2 wk, with significant proliferative glomerulonephritis at 4 wk, progressing to chronic disease with tubulointerstitial changes at 6 wk. Changes at each time period were uniform between animals. C3 mRNA was first detected by in situ hybridization at 3 wk. Message was restricted to proximal tubular and periglomerular epithelial cells. Presence of C3 message preceded the development of interstitial inflammation and fibrosis by 1-2 wk, and its location and intensity paralleled the evolving interstitial disease. Although extensive mesangial C3 protein deposits appeared early, there was never C3 message in glomeruli or infiltrating cells. Before C3 message became apparent, two cytokines known to up-regulate C3 transcription in vitro, IL-1 and IL-6, were detected by immunohistochemistry. The temporal sequence in this model is consistent with our hypothesis that local synthesis and activation of C3 in tubular epithelium is important to the interstitial component of chronic glomerulonephritis. The process is independent of the deposition of circulating complement in the glomerulus, but may be triggered by glomerular cytokines.
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PMID:Evidence of a role for local complement expression in a murine model of progressive glomerulonephritis. 1092 95

Most publications on the relationship between infection with Chlamydia pneumoniae and coronary heart disease (CHD) propose an association, but negative studies are also reported. Seroepidemiological studies vary in the use of different serological methods, different cutoff limits, different sampling times in relation to acute cardiac events, and different clinical stages of CHD. We wanted to compare three different commercially available methods for measuring Chlamydia antibodies to see how the choice of method influenced the prevalence of seropositive individuals in CHD patients and in healthy individuals and to see if sampling time in relation to an acute cardiac event or the stage of atherothrombotic disease influenced the results. Blood samples from 197 CHD patients and 197 individually matched healthy control individuals were tested at baseline and after 6 months; the mean age was 55 years in both groups, and 18% were women. Among the CHD patients, 166 were included at a median of 16 days after an acute cardiac event and 31 had chronic disease with the latest acute event being >3 months earlier. The difference in prevalence of antibodies between the CHD patients and the healthy controls was significant when Chlamydia lipopolysaccharide antibodies were measured, while no significant differences between the study groups were observed by the two methods detecting Chlamydia pneumoniae major outer membrane protein antibodies. The number of seropositive individuals was quite similar at inclusion and 6 months later, and no significant differences were observed between patients with a recent cardiac event and those with a more remote cardiac event. We conclude that the choice of serological method is of major importance when evaluating a possible relationship between C. pneumoniae and CHD.
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PMID:Chlamydia pneumoniae serology: importance of methodology in patients with coronary heart disease and healthy individuals. 1132 4

Plasma S-nitrosothiols are believed to function as a circulating form of nitric oxide that affects both vascular function and platelet aggregation. However, the formation of circulating S-nitrosothiols in relation to acute and chronic disease is largely unknown. Plasma S-nitrosothiols were measured by chemiluminescence in rats with biliary cirrhosis or controls, and the effect of lipopolysaccharide (LPS) on their formation was determined. Plasma S-nitrosothiols were increased in rats with cirrhosis (206 +/- 59 nM) compared to controls (51 +/- 6 nM, p <.001). Two hours following injection of LPS (0.5 mg/kg) plasma S-nitrosothiols increased to 108 +/- 23 nM in controls (p <.01) and to 1335 +/- 423 nM in cirrhotic rats (p <.001). The plasma clearance and half-life of S-nitrosoalbumin, the predominant circulating S-nitrosothiol, were similar in control and cirrhotic rats, confirming that the increased plasma concentrations were due to increased synthesis. Because reactive nitrogen species, such as peroxynitrite, may cause the formation of S-nitrosothiols in vivo, we determined the levels of nitrotyrosine by gas chromatography/mass spectrometry as an index for these nitrating and nitrosating radicals. Hepatic nitrotyrosine levels were increased at 7.0 +/- 1.2 ng/mg in cirrhotic rats compared to controls (2.0 +/- 0.2 ng/mg, p <.01). Hepatic nitrotyrosine levels increased by 2.3-fold and 1.5-fold in control and cirrhotic rats, respectively, at 2 h following injection of LPS (p <.01). Strong positive staining for nitrotyrosine was shown by immunohistochemistry in all the livers of the rats with cirrhosis. We conclude that there is increased formation of S-nitrosothiols and nitrotyrosine in biliary cirrhosis, and this is markedly upregulated during endotoxemia.
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PMID:Increased formation of S-nitrothiols and nitrotyrosine in cirrhotic rats during endotoxemia. 1155 17


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