Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0519030 (Klebsiella)
21,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gamma interferon (IFN-gamma) has been shown to be able to modulate several microbiol infections, perhaps as a result of the immunoregulatory properties of this interferon. The present study was designed to determine the efficacy of IFN-gamma treatment in a mouse model of infection that simulates clinical conditions occurring following abdominal trauma. In this model, mice were first infected intraperitoneally with Escherichia coli and then underwent immediate surgical laparotomy. Finally the mice were secondarily infected intramuscularly with Klebsiella pneumoniae. Groups of CBA/J mice received either IFN-gamma or RPMI 1640 medium (controls) subcutaneously. IFN-gamma was administered daily at a dose of 7,500 U, commencing 1 h postlaparotomy and continuing until the second bacterial challenge. Mice treated with IFN-gamma survived significantly longer than controls. The Ia antigen expression of peripheral blood monocytes was severely reduced in animals for 3 days after laparotomy and for 5 days after laparotomy and infection. This drop in Ia antigen expression was prevented in animals treated with IFN-gamma. These data indicate that IFN-gamma had a beneficial effect in a model simulating bacterial infection after trauma and that maintenance of Ia antigen expression in interferon-treated mice may have contributed to the observed therapeutic effect.
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PMID:Modulation of infection by gamma interferon treatment following trauma. 313 68

In a number of mammalian cell types, pteridine biosynthesis from guanosine 5'-triphosphate and formation of nitric oxide from L-arginine are induced by gamma interferon (IFN-gamma) and bacterial lipopolysaccharide (LPS). We assessed the possibility of using such metabolic alterations for the in vitro detection of pyrogens. Products from gram-negative and gram-positive bacteria and related synthetic compounds were tested for their potential to induce either of these pathways. Stimulation of pteridine biosynthesis was monitored as the formation of neopterin in the human myelomonocytic cell line THP-1. The formation of nitric oxide was determined as nitrite in murine J774A.1 macrophage cultures. The substances tested included toxic and detoxified parts of LPS and lipid A from Escherichia coli, Salmonella typhimurium, Salmonella minnesota, and Klebsiella pneumoniae as well as lipoteichoic acid and toxic shock syndrome toxin 1 from Staphylococcus aureus. Furthermore, two cell wall compounds from Mycobacterium tuberculosis, trehalose 6,6'-dimycolate and N-acetylmuramyl-L-alanyl-D-isoglutamine, which are active components of Freund's adjuvant, were used. When applied as a single stimulus, only the whole LPS molecule potently stimulated neopterin or nitrite formation. Lipid A and products from gram-positive bacteria were weakly active. For neopterin formation, lipid A required the presence of fetal calf serum. Besides detoxified LPS and independently from the presence of serum, all bacterial compounds tested strongly increased the effects mediated by IFN-gamma. Our results show that bacterial pyrogens can be detected by monitoring the formation of neopterin or nitrite. This may provide a basis for the development of an in vitro assay for the detection of pyrogenic contamination with the aim of replacing the currently used animal test.
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PMID:Detection of bacterial pyrogens on the basis of their effects on gamma interferon-mediated formation of neopterin or nitrite in cultured monocyte cell lines. 766 77

Activation of the host defense system in a nonspecific way might provide tools to support failing antibiotic treatment in certain infectious diseases. The antimicrobial effect was investigated of liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (MTPPE) and interferon (IFN)-gamma and liposome-coencapsulated MTPPE and IFN-gamma on Klebsiella pneumoniae septicemia in mice. Prophylactic treatment of mice with five doses of liposomal MTPPE or IFN-gamma increased survival from 0 to 65%. Administration of MTPPE and IFN-gamma coencapsulated in liposome resulted in 100% survival. In vitro, peritoneal macrophages by themselves were stimulated by these agents but were unable to kill K. pneumoniae. However, production of both oxygen and nitrogen intermediates increased when immunomodulators were added to macrophages. These results indicate that effective prophylactic treatment of septicemia due to K. pneumoniae with coencapsulated MTPPE and IFN-gamma is not solely due to activation of the resident macrophages.
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PMID:Modulation of nonspecific antimicrobial resistance of mice to Klebsiella pneumoniae septicemia by liposome-encapsulated muramyl tripeptide phosphatidylethanolamine and interferon-gamma alone or combined. 784 75

IL-12 is a proinflammatory cytokine that has recently been shown to have beneficial effects in the setting of acquired host immunity. To determine the role of IL-12 in innate immunity against Gram-negative bacterial organisms, CBA/J mice were challenged with 10(2) CFU of Klebsiella pneumoniae intratracheally (i.t.), resulting in the time-dependent expression of IL-12 mRNA (p35 and p40) and protein within the lung. Passive immunization of animals with anti-IL-12 serum i.p. at the time of K. pneumoniae inoculation resulted in a 12-fold increase in K. pneumoniae CFU in lung homogenates at 48 h, as compared with animals receiving control serum. In addition, treatment of Klebsiella-infected mice with anti-IL-12 Abs significantly decreased both short and long term survival. To assess the effect of compartmentalized IL-12 overexpression on outcome in Klebsiella pneumonia, animals were treated i.t. with 5 x 10(8) PFU of a nonreplicating adenoviral vector containing a human cytomegalovirus promoter and cDNAs coding for the p35 and p40 subunits of IL-12 inserted into the E1 and E3 domains (Ad5mIL-12), respectively. In vivo transfection with Ad5mIL-12 resulted in 45% long term survival in Klebsiella pneumonia, whereas no animals with Klebsiella pneumonia receiving control adenovirus survived. Moreover, treatment with anti-IFN-gamma Abs or soluble TNF receptor:Ig construct partially and completely attenuated survival benefits observed in animals receiving Ad5mIL-12, respectively. In conclusion, endogenous IL-12 is a critical component of antibacterial host defense, and the compartmentalized overexpression of IL-12 using recombinant adenoviral gene therapy represents a safe and effective approach to deliver IL-12 to the lung in the setting of murine Klebsiella pneumonia.
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PMID:IL-12 gene therapy protects mice in lethal Klebsiella pneumonia. 881 9

We have previously shown that prophylactic administration of the liposome-encapsulated immunomodulating agents muramyl tripeptide phosphatidylethanolamine (MTPPE) and gamma interferon (IFN-gamma) results in strongly increased survival of mice from a normally lethal septicemia with Klebsiella pneumoniae. It was anticipated that the treatment acts on macrophages and nonspecifically augments host resistance to various infections. In the present study, we provide evidence for a key role for T cells in host defense potentiation by the liposomal immunomodulators toward K. pneumoniae septicemia. It is shown that both CD4 and CD8 cells are important in immunomodulation, most likely due to production of IFN-gamma. Depletion of circulating IFN-gamma resulted in strong reduction of the antimicrobial host defense activation. Administration of interleukin-10 resulted in decreased antimicrobial host defense activation by liposomal immunomodulators. Moreover, administration of liposomal immunomodulators was shown to induce predominantly T-helper type 1 (Th1) cell populations in the spleen. These findings indicate that immunomodulation with liposomal MTPPE and IFN-gamma favors Th1 and NK cell activation.
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PMID:Involvement of T cells in enhanced resistance to Klebsiella pneumoniae septicemia in mice treated with liposome-encapsulated muramyl tripeptide phosphatidylethanolamine or gamma interferon. 957 76

A vigorous host response is required to effectively clear pathogenic bacteria from the lungs and is dependent upon the recruitment and activation of neutrophils and macrophages. A family of chemotactic cytokines, referred to as chemokines, have been shown to participate in this complex protective response. In this study, we assessed the role of the C-X-C chemokine KC in lung antibacterial host defense using wild-type (wt) B6D2 mice or transgenic mice that had been bred on a B6D2 background expressing KC under the control of a Clara cell-specific promoter within the lung. The administration of Klebsiella pneumoniae to both wt and KC-transgenic mice resulted in a time-dependent expression of KC protein within the lung that peaked at 24 to 48 h postinoculation. When infected with K. pneumoniae, the KC-transgenic mice showed a striking improvement in survival compared with wt control mice. This improved survival was due to an increase in bacterial clearance, which occurred in association with a vigorous recruitment of neutrophils in the KC-transgenic mice compared with their wt control counterparts. No differences in the lung levels of the specific cytokines TNF-alpha, IFN-gamma, IL-12, and IL-10 were noted. However, inducible macrophage inflammatory protein-2 levels were significantly decreased in the KC-transgenic mice compared with the wt mice. This study indicates that the compartmentalized overexpression of KC in vivo results in increased lung bacterial clearance and improved survival, which occurs in association with enhanced polymorphonuclear leukocyte influx to the lung.
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PMID:Lung-specific transgenic expression of KC enhances resistance to Klebsiella pneumoniae in mice. 972 41

We investigated whether oral administration of LPS exacerbated collagen-induced arthritis (CIA) in mice, which was an experimental model of autoimmune disease. CIA was induced by s.c. injection of type II collagen emulsified with CFA into the base of the tail (day 0) followed by a booster injection on day 21. To examine the ability of LPS to exacerbate CIA, varying doses of LPS were orally administered on day 50. The results showed that administration of LPS was followed by reactivation of CIA in a dose-related fashion. Histologically, on day 55 there were marked edema of synovium proliferated by day 50, new formation of fibrin, and intense infiltration of neutrophils accompanied with a large number of mononuclear cells. Severe destruction of cartilage and subchondral bone was also observed on day 70. The reactivation of CIA by oral administration of LPS was associated with increase in anti-type II collagen IgG and IgG2a Abs as well as varying kinds of cytokines including IL-12, IFN-gamma, IL-1beta, and TNF-alpha. Polymyxin B sulfate given either orally or i.v. suppressed the recurrence of CIA. Increased amounts of LPS were found in sera of mice given the endotoxin orally. LPS from Salmonella enteritidis, Salmonella typhimurium, and Klebsiella pneumoniae and its component, lipid A from Escherichia coli, also reactivated the disease. These findings suggest that LPS from intestinal bacteria may play a role in the exacerbation of autoimmune joint inflammation.
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PMID:Oral administration of lipopolysaccharide exacerbates collagen-induced arthritis in mice. 1047 13

Outer membrane protein (Omp)A is highly represented and conserved in the Enterobacteriaceae family. Using a recombinant OmpA from Klebsiella pneumoniae (P40), we have analyzed the interaction between OmpA and macrophages. We report that Alexa488-labeled P40 binds (at 4 degrees C) to murine and human macrophages in a dose-dependent manner and is rapidly internalized (at 37 degrees C). No binding or internalization of the Alexa488-labeled glycophorin A control protein is observed under the same conditions. Furthermore, P40 up-regulates the production of IL-1beta, IL-8, IL-10, IL-12, and TNF-alpha by human macrophages and of NO by the RAW 264.7 murine macrophage cell line. P40 also synergizes with IFN-gamma and suboptimal concentrations of LPS to up-regulate the production of these mediators. In conclusion, P40 binds to and activates macrophages. These data suggest that recognition of OmpA by macrophages may be an initiating event in the antibacterial host response.
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PMID:Outer membrane protein A (OmpA) binds to and activates human macrophages. 1094 55

Although cells of the innate inflammatory response, such as macrophages and neutrophils, have been extensively studied in the arena of Gram-negative bacterial pneumonia, a role for T cells remains unknown. To study the role of specific T cell populations in bacterial pneumonia, mice deleted of their TCR beta- and/or delta-chain were intratracheally inoculated with Klebsiella pneumoniae. Gamma delta T cell knockout mice displayed increased mortality at both early and late time points. In contrast, mice specifically lacking only alpha beta-T cells were no more susceptible than wild-type mice. Pulmonary bacterial clearance in gamma delta-T cell knockout mice was unimpaired. Interestingly, these mice displayed increased peripheral blood dissemination. Rapid up-regulation of IFN-gamma and TNF-alpha gene expression, critical during bacterial infections, was markedly impaired in lung and liver tissue from gamma delta-T cell-deficient mice 24 h postinfection. The increased peripheral blood bacterial dissemination correlated with impaired hepatic bacterial clearance following pulmonary infection and increased hepatic injury as measured by plasma aspartate aminotransferase activity. Combined, these data suggest that mice lacking gamma delta-T cells have an impaired ability to resolve disseminated bacterial infections subsequent to the initial pulmonary infection. These data indicate that gamma delta-T cells comprise a critical component of the acute inflammatory response toward extracellular Gram-negative bacterial infections and are vital for the early production of the proinflammatory cytokines IFN-gamma and TNF-alpha.
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PMID:Gamma delta-T cells are critical for survival and early proinflammatory cytokine gene expression during murine Klebsiella pneumonia. 1094 93

Collagen-induced arthritis (CIA) is an excellent model of rheumatoid arthritis (RA) in humans that is induced in DBA/1 mice immunized with bovine type II collagen (CII). Here, we report that the induction of CIA was effectively suppressed by oral administration of AZ-9, a purified polysaccharide with the average molecular weight of approximately 200 kDa that was produced by a soil bacterium, Klebsiella oxytoca. When AZ-9 was administered at 125-250 mg/kg/day orally for 9 consecutive days after immunization with CII followed by its administration every 3 days, resulted in a marked reduction of the incidence and the severity of CIA. The serum level of anti-CII IgG2a and the production of IFN-gamma and IL-12 in the draining lymph node (LN) cells were significantly lower in AZ-9-administered mice than the untreated control. These findings suggest that orally administered AZ-9 suppressed CIA through attenuating a Th1-type response to CII. AZ-9 could be fragmented into smaller molecules (3-4 kDa) without losing its suppressive activity.
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PMID:Prevention of collagen-induced arthritis in DBA/1 mice by oral administration of AZ-9, a bacterial polysaccharide from Klebsiella oxytoca. 1099 30


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