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Production of granulocyte colony-stimulating factor in the nonspecific acute phase response enhances host resistance to bacterial infection 总被引:3,自引:0,他引:3
Noursadeghi M Bickerstaff MC Herbert J Moyes D Cohen J Pepys MB 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(2):913-919
Mice mounting an acute phase response, induced by sterile inflammation after a single s.c. injection of casein 24 h beforehand, were remarkably protected against lethal infection with Gram-positive or Gram-negative bacteria. This was associated with enhanced early clearance of bacteremia, greater phagocytosis and oxidative burst responses by neutrophils, and enhanced recruitment of neutrophils into tissues compared with control, nonacute phase mice. Casein-induced inflammation was also associated with increased concentrations of G-CSF in serum, and administration of neutralizing Ab to this cytokine completely abrogated protection against Escherichia coli infection after casein pretreatment. Injection of recombinant murine G-CSF between 3 and 24 h before infection conferred the same protection as casein injection. In contrast, the casein-induced acute phase response affected neither serum values of TNF-alpha, IL-1 beta, or IL-6 after E. coli infection nor susceptibility to LPS toxicity. Furthermore, protection against infection was unaffected in IL-1R knockout mice, which have deficient acute phase plasma protein responses, or after nonspecific inhibition of acute phase protein synthesis by D-galactosamine or specific depletion of complement C3 by cobra venom factor. Increased production of G-CSF in the acute phase response is thus a key physiological component of host defense, and pretreatment with G-CSF to prevent bacterial infection in at-risk patients now merits further study, especially in view of increasing bacterial resistance to antibiotics. 相似文献
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Stewart SG Spagnolo D Polomska ME Sin M Karimi M Abraham LJ 《Bioorganic & medicinal chemistry letters》2007,17(21):5819-5824
A library of new thalidomide analogues containing an olefin functionality were synthesised using a Heck cross coupling reaction from their aryl halogenated precursor. All analogues were tested for their ability to inhibit the synthesis of the proinflammatory cytokine Tumour Necrosis Factor (TNF). Compounds 22, 29, 33 and 37 were the most effective in this assay inhibiting TNF expression 50%, 69%, 52% and 50%, respectively. 相似文献
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Shimizu A Baratchian M Takeuchi Y Escors D Macdonald D Barrett T Bagneris C Collins M Noursadeghi M 《Journal of virology》2011,85(14):7444-7448
Activation of IκB kinase subunit γ (IKKγ), a key regulator of the classical NF-κB pathway, by the vFLIP protein of Kaposi's sarcoma-associated herpesvirus (KSHV) and the Tax protein of human T cell lymphotropic virus type 1 (HTLV1) is essential for virus-associated cancer. We show that vFLIP and Tax activate this pathway by different interactions with IKKγ and independently of the ubiquitin-mediated signaling pathways induced by cytokines. Our data provide new insights into the mechanisms by which IKKγ can be activated and show that NF-κB activation by oncogenic viruses can be targeted without affecting physiologically important pathways. 相似文献
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Laura M. J. Ylinen Torsten Schaller Amanda Price Adam J. Fletcher Mahdad Noursadeghi Leo C. James Greg J. Towers 《Journal of virology》2009,83(4):2044-2047
Cyclophilin A (CypA) is an important human immunodeficiency virus type 1 (HIV-1) cofactor in human cells. HIV-1 A92E and G94D capsid escape mutants arise during CypA inhibition and in certain cell lines are dependent on CypA inhibition. Here we show that dependence on CypA inhibition is due to high CypA levels. Restricted HIV-1 is stable, and remarkably, restriction is augmented by arresting cell division. Nuclear entry is not inhibited. We propose that high CypA levels and capsid mutations combine to disturb uncoating, leading to poor infectivity, particularly in arrested cells. Our data suggest a role for CypA in uncoating the core of HIV-1 to facilitate integration. 相似文献
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Collini P Noursadeghi M Sabroe I Miller RF Dockrell DH 《Current molecular medicine》2010,10(8):727-740
HIV-1 can establish both long lived and productive infection of macrophages (M?) but circulating monocytes are less permissive to infection. Multiple studies have identified extensive changes to monocyte and M? phenotype, differentiation or function. These include alterations in Toll-like receptor signaling and resultant changes to cytokine responses, specific defects in phagocytosis and microbial killing and modulation of apoptotic responses, all of which may perturb the important role of these cells in innate immunity. Interpretation of contradictory data however, is complicated by the use of different experimental models and many of the reported effects may be an indirect consequence of HIV 1 infection that result from exposure to viral products or from disruption of cellular and cytokine networks in the immune system, rather than the direct consequence of productive HIV 1 infection. Future research should focus on refining experimental models and on elucidating the physiological mechanisms of monocyte/ M? dysfunction during HIV 1 infection. 相似文献