Linked Life Data

21896016

Source:http://linkedlifedata.com/resource/pubmed/id/21896016

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pubmed-article:21896016pubmed:abstractTextB-cell activation factor of the tumour necrosis factor family (BAFF), an important regulator of B-cell survival, has recently been found to be expressed on the surface of murine and human macrophages and engagement with its receptor was shown to trigger induction of pro-inflammatory mediators and block phagocytic activity. In an effort to generate immunomodulatory agents that can regulate BAFF-mediated signal, decapeptides representing the intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs) of immune receptor expressed on myeloid cells (IREM)-1, an inhibitory transmembrane protein expressed on myeloid cells, were synthesized in conjugation with HIV-transactivator of transcription (TAT)(48-57,) which facilitates the internalization of peptides into cells. Interestingly, all five of these synthetic peptides, representing the five ITIM-like sequences present in the cytoplasmic tail of IREM-1, exhibited inhibitory action against BAFF-mediated induction of matrix metalloproteinase-9 and interleukin-8 expression. Inhibitor assay and immunoprecipitation assay followed by Western blotting demonstrated that the inhibitory action was mediated by Src homology 2 (SH2)-containing tyrosine phosphatase (SHP)-1 and/or phosphoinositide 3-kinase (PI3K). ELISA-based nuclear factor-?B DNA binding assay observed that the synthetic peptides blocked the activation of nuclear factor-?B in an SHP-1 and phosphoinositide 3-kinase-dependent manner. Three of these synthetic peptides exhibited varying degrees of inhibitory action against BAFF-mediated blockage of phagocytosis in a SHP-1 and PI3K-dependent manner. These data indicate that the synthetic peptides are capable of blocking BAFF-mediated regulation of macrophage activities through the activation of SHP-1 and PI3K as well as inhibition of nuclear factor-?B activation.lld:pubmed
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pubmed-article:21896016pubmed:authorpubmed-author:LeeWon-HaWHlld:pubmed
pubmed-article:21896016pubmed:authorpubmed-author:SukKyounghoKlld:pubmed
pubmed-article:21896016pubmed:authorpubmed-author:LeeSang-MinSMlld:pubmed
pubmed-article:21896016pubmed:authorpubmed-author:KimEun-JuEJlld:pubmed
pubmed-article:21896016pubmed:copyrightInfo© 2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd.lld:pubmed
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pubmed-article:21896016pubmed:volume134lld:pubmed
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pubmed-article:21896016pubmed:year2011lld:pubmed
pubmed-article:21896016pubmed:articleTitleSynthetic peptides containing ITIM-like sequences of IREM-1 inhibit BAFF-mediated regulation of interleukin-8 expression and phagocytosis through SHP-1 and/or PI3K.lld:pubmed
pubmed-article:21896016pubmed:affiliationSchool of Life Sciences and Biotechnology, Kyungpook National University, Daegu, Korea.lld:pubmed
pubmed-article:21896016pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:21896016pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed