| Pathway-selective suppression of chemokine receptor signaling in B cells by LPS through downregulation of PLC-β2. | |
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MedLine Citation:
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PMID: 20871625 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Lymphocyte activation leads to changes in chemokine receptor expression. There are limited data, however, on how lymphocyte activators can alter chemokine signaling by affecting downstream pathways. We hypothesized that B cell-activating agents might alter chemokine responses by affecting downstream signal transducers, and that such effects might differ depending on the activator. We found that activating mouse B cells using either anti-IgM or lipopolysaccharide (LPS) increased the surface expression of CCR6 and CCR7 with large increases in chemotaxis to their cognate ligands. By contrast, while anti-IgM also led to enhanced calcium responses, LPS-treated cells showed only small changes in calcium signaling as compared with cells that were freshly isolated. Of particular interest, we found that LPS caused a reduction in the level of B-cell phospholipase C (PLC)-β2 mRNA and protein. Data obtained using PLC-β2(-/-) mice showed that the β2 isoform mediates close to one-half the chemokine-induced calcium signal in resting and anti-IgM-activated B cells, and we found that calcium signals in the LPS-treated cells were boosted by increasing the level of PLC-β2 using transfection, consistent with a functional effect of downregulating PLC-β2. Together, our results show activator-specific effects on responses through B-cell chemokine receptors that are mediated by quantitative changes in a downstream signal-transducing protein, revealing an activity for LPS as a downregulator of PLC-β2, and a novel mechanism for controlling chemokine-induced signals in lymphocytes. |
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Authors:
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Aiko-Konno Shirakawa; Fang Liao; Hongwei H Zhang; Michael N Hedrick; Satya P Singh; Dianqing Wu; Joshua M Farber |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Intramural Date: 2010-09-27 |
Journal Detail:
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Title: Cellular & molecular immunology Volume: 7 ISSN: 2042-0226 ISO Abbreviation: Cell. Mol. Immunol. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-02 Completed Date: 2011-03-02 Revised Date: 2012-05-04 |
Medline Journal Info:
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Nlm Unique ID: 101242872 Medline TA: Cell Mol Immunol Country: China |
Other Details:
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Languages: eng Pagination: 428-39 Citation Subset: IM |
Affiliation:
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Inflammation Biology Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals B-Lymphocytes / cytology, drug effects*, enzymology*, immunology Calcium / metabolism Calcium Signaling / drug effects Chemokines / pharmacology Cyclic AMP-Dependent Protein Kinases / metabolism Down-Regulation / drug effects* Gene Expression Regulation, Enzymologic / drug effects Immunoglobulin M / immunology Lipopolysaccharides / pharmacology* Lymphocyte Activation / drug effects Mice Models, Immunological Phospholipase C beta / genetics, metabolism* RNA, Messenger / genetics, metabolism Receptors, Chemokine / metabolism* Signal Transduction / drug effects*, immunology Type C Phospholipases / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 GM054597/GM/NIGMS NIH HHS; R01 HL080706-15/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chemokines; 0/Immunoglobulin M; 0/Lipopolysaccharides; 0/RNA, Messenger; 0/Receptors, Chemokine; 7440-70-2/Calcium; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases; EC 3.1.4.-/Type C Phospholipases; EC 3.1.4.11/Phospholipase C beta |
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