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      <title>Tumor necrosis factor and caspase in response to soluble or microparticle-incorporated drugs in Mycobacterium tuberculosis infection</title>
      <link>http://dx.doi.org/10.1038/npre.2007.1190.1</link>
      <description>We compared the effects of microparticles (MP) containig anti-tubercular drugs and those of the drugs themselves on the host macrophage (M&#934;) response to infection with Mycobacterium tuberculosis H37Ra (Mtb). Mice infected intravenously with M. tb. were either administered rifampicin and isoniazid by oral gavage or through inhalation of biodegradable MP containing the two anti-tubercular drugs. Bronchoalveolar lavage (BAL) was perfomed to recover lung M&#934;, which were cultured and the supernatant analysed for TNF&#945; by ELISA. The murine M&#934; cell line J774 or the human monocyte line THP-1 differentiated with phorbol myristate were infected in vitro and treated with MP or soluble drugs. The kinetics of secretion of TNF&#945; were determined. Caspase-3 activity after infection and treatment was assesed using a substrate cleavage detection kit.MP, but not soluble drugs, strongly induced TNF&#945; in infected cells. Uninfected cells also responded to MP, although less strongly. Caspase-3 was observed to be upregulatedWe conclude that MP treatment induces infected M&#934; to upregulate the Th1 cytokine TNF&#945; and Caspase-3, creating conditions for induction of apoptosis in these cells as a strategy to overcome infection.</description>
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      <pubDate>Sun, 30 Sep 2007 20:17:49 UTC</pubDate>
      <dc:title>Tumor necrosis factor and caspase in response to soluble or microparticle-incorporated drugs in Mycobacterium tuberculosis infection</dc:title>
      <dc:identifier>doi:10.1038/npre.2007.1190.1</dc:identifier>
      <dc:date>2007-09-30</dc:date>
      <dc:creator>Amit Misra</dc:creator>
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      <prism:publicationDate>2007-09-30T20:17:49Z</prism:publicationDate>
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      <prism:section>Immunology</prism:section>
      <prism:section>Pharmacology</prism:section>
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      <title>Synergistic Induction of NR4A Orphan Nuclear Receptors by LPS and cAMP in Murine Macrophage Cells</title>
      <link>http://dx.doi.org/10.1038/npre.2007.663.1</link>
      <description>Although NR4A orphan nuclear receptors have been implicated in inflammatory gene expression and atherosclerosis, there is little information regarding their regulation by combinations of stimuli likely to be found in vivo, such as LPS and inducers of cAMP. LPS rapidly induced Nur77 and NOR1 mRNAs but had little effect on expression of Nurr1 mRNA. All three NR4As were rapidly induced by 8-bromo-cAMP and remained elevated for at least 8 h. Maximum induction of NOR1 by 8-bromo-cAMP was much greater than with LPS, but maximum induction of Nur77 was similar with both agents. Whereas Nurr1 mRNA had very little response to LPS, it was strongly induced by 8-bromo-cAMP, and Nurr1 mRNA levels remained elevated for at least 20 h. The combination of 8-bromo-cAMP and LPS acted synergistically to strongly induce NOR1 and Nur77, whereas LPS partially inhibited the induction of Nurr1 by 8-bromo-cAMP. Nurr1 protein levels correlated with Nurr1 mRNA levels but exhibited slower response kinetics. In summary, the NR4A receptors did not respond identically to individual stimuli or to combinations of stimuli. In particular, the magnitude of the responses to combinations of stimuli was quite different than to individual stimuli. Thus, NR4A receptor expression and the resulting functional consequences are more complex than appreciated from previous studies that evaluated regulation of NR4A expression by single stimuli.</description>
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      <pubDate>Fri, 10 Aug 2007 09:00:06 UTC</pubDate>
      <dc:title>Synergistic Induction of NR4A Orphan Nuclear Receptors by LPS and cAMP in Murine Macrophage Cells</dc:title>
      <dc:identifier>doi:10.1038/npre.2007.663.1</dc:identifier>
      <dc:date>2007-08-10</dc:date>
      <dc:creator>Sidney M. Morris</dc:creator>
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      <prism:publicationDate>2007-08-10T09:00:06Z</prism:publicationDate>
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      <prism:section>Molecular Cell Biology</prism:section>
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      <title>LipidMaps Core Update</title>
      <link>http://dx.doi.org/10.1038/npre.2007.23.1</link>
      <description>LipidMaps (http://www.lipidmaps.org) is a multidisciplinary project involving multiple institutions. The goal of this project is to identify lipid metabolites and reconstruct pathways associated with lipids in mammalian cells using quantitative measurements of lipids in macrophage cells. </description>
      <guid>http://dx.doi.org/10.1038/npre.2007.23.1</guid>
      <pubDate>Tue, 23 Jan 2007 04:01:48 UTC</pubDate>
      <dc:title>LipidMaps Core Update</dc:title>
      <dc:identifier>doi:10.1038/npre.2007.23.1</dc:identifier>
      <dc:date>2007-01-23</dc:date>
      <dc:creator>Shankar Subramaniam</dc:creator>
      <prism:publicationName>Nature Precedings</prism:publicationName>
      <prism:publicationDate>2007-01-23T04:01:48Z</prism:publicationDate>
      <prism:category>Presentation</prism:category>
      <prism:section>Bioinformatics</prism:section>
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