Document Detail


A novel cell-cell signaling by microglial transmembrane TNFα with implications for neuropathic pain.
MedLine Citation:
PMID:  20609516     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Neuropathic pain is accompanied by neuroimmune activation in dorsal horn of spinal cord. We have observed that in animal models this activation is characterized by an increased expression of transmembrane tumor necrosis factor α (mTNFα) without the release of soluble tumor necrosis factor α (sTNFα). Herein we report that the pain-related neurotransmitter peptide substance P (SP) increases the expression of mTNFα without the release of sTNFα from primary microglial cells. We modeled this interaction using an immortalized microglial cell line; exposure of these cells to SP also resulted in the increased expression of mTNFα but without any increase in the expression of the TNF-cleaving enzyme (TACE) and no release of sTNFα. In order to evaluate the biological function of uncleaved mTNFα, we transfected COS-7 cells with a mutant full-length TNFα construct resistant to cleavage by TACE. Coculture of COS-7 cells expressing the mutant TNFα with microglial cells led to microglial cell activation indicated by increased OX42 immunoreactivity and release of macrophage chemoattractant peptide 1 (CCL2) by direct cell-cell contact. These results suggest a novel pathway through which the release of SP by primary afferents activates microglial expression of mTNFα, establishing a feed-forward loop that may contribute to the establishment of chronic pain.
Authors:
Zhigang Zhou; Xiangmin Peng; Jafar Hagshenas; Ryan Insolera; David J Fink; Marina Mata
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-07-06
Journal Detail:
Title:  Pain     Volume:  151     ISSN:  1872-6623     ISO Abbreviation:  Pain     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-15     Completed Date:  2011-02-14     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  7508686     Medline TA:  Pain     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  296-306     Citation Subset:  IM    
Copyright Information:
Published by Elsevier B.V.
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MeSH Terms
Descriptor/Qualifier:
ADAM Proteins / genetics,  metabolism
Animals
Animals, Newborn
Brain / cytology
COS Cells / physiology
Cell Communication / genetics,  physiology*
Cells, Cultured
Cercopithecus aethiops
Coculture Techniques
Enzyme Inhibitors / pharmacology
Enzyme-Linked Immunosorbent Assay / methods
Gene Expression Regulation / drug effects,  genetics
Green Fluorescent Proteins / genetics
Hydroxamic Acids / pharmacology
Lipopolysaccharides / pharmacology
Microglia / cytology,  drug effects,  physiology*
RNA, Small Interfering / metabolism
Rats
Signal Transduction / genetics,  physiology*
Substance P / pharmacology
Transfection / methods
Tumor Necrosis Factor-alpha / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
P01 DK044935/DK/NIDDK NIH HHS; R01 NS038850/NS/NINDS NIH HHS; R01 NS038850-09/NS/NINDS NIH HHS; R01 NS038850-10/NS/NINDS NIH HHS; R01 NS038850-11/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Hydroxamic Acids; 0/Lipopolysaccharides; 0/RNA, Small Interfering; 0/TAPI-2; 0/Tumor Necrosis Factor-alpha; 147336-22-9/Green Fluorescent Proteins; 33507-63-0/Substance P; EC 3.4.24.-/ADAM Proteins; EC 3.4.24.-/tumor necrosis factor-alpha convertase
Comments/Corrections
Comment In:
Pain. 2010 Nov;151(2):241-2   [PMID:  20739122 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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