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Release of tumor necrosis factor-á from macrophages is mediated by small GTPase Rab37.
MedLine Citation:
PMID:  21805469     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Activated macrophages at wound sites release many cytokines, which positively affect skin wound healing. However, the molecular mechanisms controlling cytokine secretion from macrophages have not been elucidated. In the present study, we performed an RT-PCR analysis and found that 19 small GTPase Rab isoforms were expressed at skin wound sites, with six of them (i.e., Rab3B, Rab27B, Rab30, Rab33A, Rab37, and Rab40C) being up-regulated during the inflammation and proliferation/migration phase of skin repair. We also found that gene expression of Rab37 in murine primary and RAW264.7 macrophage cells were significantly induced after stimulation with LPS. Overexpression of wild type and constitutively active Rab37 in RAW264.7 cells significantly increased TNFα secretion, whereas knockdown of Rab37 by siRNA significantly decreased it. We also identified 29 putative Rab37-interacting proteins, including the membrane fusion regulating Munc13-1, using liquid chromatography/linear ion trap mass spectrometry (LC-MS/MS). Immunocytochemical analysis further revealed that TNFα-containing vesicles were colocalized with both Rab37 and Munc13-1 in activated macrophages. Knockdown of Munc13-1 by siRNA significantly decreased TNFα secretion. Taken together, these findings demonstrated that Rab37 interacts with Munc13-1 to control TNFα secretion from activated macrophages.
Authors:
Ryoichi Mori; Kazuya Ikematsu; Tetsuya Kitaguchi; Sang Eun Kim; Momoko Okamoto; Takuya Chiba; Atsushi Miyawaki; Isao Shimokawa; Takashi Tsuboi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-8-1
Journal Detail:
Title:  European journal of immunology     Volume:  -     ISSN:  1521-4141     ISO Abbreviation:  -     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-8-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Affiliation:
Departments of Investigative Pathology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan.
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