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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Chloroquine, an antimalarial lysosomotropic base, is known for its anti-inflammatory effects and therefore used for treatment of autoimmune diseases. Given its anti-inflammatory effects, it has been under clinical trials to modify neurodegenerative processes. In this study, we examined whether chloroquine has an anti-inflammatory effect in the CNS by determining the in vitro effects of chloroquine on LPS-induced expression of cytokines by glial cells. We observed that (i) chloroquine augmented LPS-induced expression of pro-inflammatory cytokines such as lymphotoxin (LT)-β, tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1β and IL-6 in human astroglial cells, while the same treatment suppressed LPS-induced expression of cytokines in monocytic and microglial cells; (ii) chloroquine alone induced expression of pro-inflammatory cytokines in a dose- and time-dependent manner in astroglial cells; (iii) other lysosomotropic agents such as ammonium chloride and bafilomycin A1 had minimal effects on cytokine expression; and (iv) chloroquine induced the activation of nuclear factor-kappa B in astroglial cells, which is a required component of chloroquine induction of cytokines. These results suggest that chloroquine may evoke either anti- or pro-inflammatory responses in the CNS depending on the cellular context.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0219-1032
    Keywords: Alternative Splicing ; NK Cells ; p70 KIR ; Polymorphism ; Receptor Repertoire
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract NK cells and some T cells express members of a multigenic family of killer cell inhibitory receptors (KIRs) including p70 KIR (KIR3DL) and p58 KIR (KIR2DL) family that recognize polymorphic class I MHC molecules on target cells and transmit an inhibitory signal to prevent killer cell-mediated cytoxicity. The cDNA sequences of p70 KIR family members reported so far suggest that the p70 KIR gene consists of a multigene complex and that each gene may exhibit certain degrees of polymorphism. However, it is not clear how diverse the repertoire of the p70 KIR family is, particularly in a single individual. To address this question in more detail and to determine some indication as to the origin of the diversity, we cloned p70 KIR cDNAs from a single individual. We identified nine new KIRs that are different from the previously reported ones. A comparison of the amino acid sequences with published sequences of p70 KIRs showed that two clones belonged to the KIR3DL1 family, five clones belonged to the KIR3DL2 family, one clone belonged to the KIR2DL4 family, and one clone appeared to be an alternatively spliced form of p70 KIR. These results suggested that the repertoire of p70 KIR family members in a single individual is highly diverse. It is not clear how the diverse receptors are generated in a single individual, but a comparison of amino acid sequences of p70 KIR family members suggested that some of them may be encoded by distinct genes or their alleles, while others may be generated by a recombination mechanism and/or an alternative splicing mechanism at the maturation of the mRNA transcripts.
    Type of Medium: Electronic Resource
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