|
|
|
|
|
|
Human Immunodeficiency Virus Type 1 Protease Inhibitors Block Toll-Like Receptor 2 (TLR2)- and TLR4-Induced NF-  B Activation.Ozlem Equils, 2004.Coinfections with opportunistic and pathogenic bacteria induce human immunodeficiency virus (HIV) replication through microbial antigen activation of NF- B . Here, we assessed whether HIV type 1 protease inhibitors (PI) block microbial antigen activation of NF-B . Human microvessel endothelial cells were transiently transfected with either endothelial cell-leukocyte adhesion molecule NF-B luciferase or interleukin 6 (IL-6) promoter luciferase constructs by using FuGENE 6, and they were treated with PI (nelfinavir, ritonavir, or saquinavir) prior to stimulation with the Toll-like receptor 4 (TLR4) and TLR2 ligands, with lipopolysaccharide (LPS), soluble Mycobacterium tuberculosis factor, or Staphylococcus epidermidis phenol-soluble modulin, respectively, or with tumor necrosis factor alpha (TNF- ) . Luciferase activity was measured by using a Promega luciferase kit . TNF- release from the supernatant was measured by enzyme-linked immunosorbent assay . Cell death was assessed by lactate dehydrogenase assay . We observed that PI pretreatment blocked the TLR2- and TLR4- as well as the TNF--mediated NF-B activation, in a dose-dependent manner . PI pretreatment also blocked the LPS-induced IL-6 promoter transactivation and TNF- secretion . These data suggest that PI block HIV replication not only by inhibiting the HIV protease but also by blocking the TLR- and TNF--mediated NF-B activation and proinflammatory cytokine production . These findings may help explain the immunomodulatory effects of PI, and they suggest an advantage for PI-containing drug regimens in the treatment of HIV-infected patients who are coinfected with opportunistic and pathogenic bacteria .
Functional and Structural Characterization of the Genetic Environment of an Extended-Spectrum ß-Lactamase blaVEB Gene from a Pseudomonas aeruginosa Isolate Obtained in India. Daniel Aubert, 2004.A Pseudomonas aeruginosa clinical strain isolated from a patient hospitalized in a New Delhi, India, hospital was resistant to expanded-spectrum cephalosporins, imipenem, and aztreonam . A blaVEB-1-like gene named blaVEB-1a, which codes for the extended-spectrum ß-lactamase VEB-1a, was identified . The genetic environment of blaVEB-1a was peculiar: (i) no 5' conserved sequence (5'-CS) region was present upstream of the ß-lactamase gene, whereas blaVEB-1-like genes are usually associated with class 1 integrons; (ii) blaVEB-1a was inserted between two truncated 3'-CS regions in a direct repeat; and (iii) four 135-bp repeated DNA sequences (repeated elements) were located on each side of the blaVEB-1a gene . Expression of the blaVEB-1a gene was driven by a strong promoter located in one of these repeated sequences . In addition, cloning of the ß-lactamase content of this P . aeruginosa isolate followed by expression in Escherichia coli identified the naturally occurring AmpC ß-lactamase and a gene encoding an OXA-2-like ß-lactamase located in a class 1 integron, In78, in which an insertion sequence, ISpa7, was inserted within its 5'-CS region . Structures of Naturally Occurring Circular Proteins from Bacteria. David J. Craik, 2003.
|
© 2005
Transgalactic Ltd (manufacturer of Bioscreen C software) |
Privacy Statement | P.O. Box
1393, 00101 Helsinki, Finland,
Last modified: May 25, 2005
| ||||||
