E3 ubiquitin ligase Cblb regulates the acute inflammatory response underlying lung injury.

E3 ubiquitin ligase Cblb regulates the acute inflammatory response underlying lung injury. Research Abstract Details 

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E3 ubiquitin ligase Cblb regulates the acute inflammatory response underlying lung injury. Abstract Text:

Kurt Bachmaier,Sophie Toya,Xiaopei Gao,Thomas Triantafillou,Sean Garrean,Gye Young Park,Randall S Frey,Stephen Vogel,Richard Minshall,John W Christman,Chinnaswamy Tiruppathi,Asrar B Malik,

The E3 ubiquitin ligase Cblb has a crucial role in the prevention of chronic inflammation and autoimmunity. Here we show that Cblb also has an unexpected function in acute lung inflammation. Cblb attenuates the sequestration of inflammatory cells in the lungs after administration of lipopolysaccharide (LPS). In a model of polymicrobial sepsis in which acute lung inflammation depends on the LPS receptor (Toll-like receptor 4, TLR-4), the loss of Cblb expression accentuates acute lung inflammation and reduces survival. Loss of Cblb significantly increases sepsis-induced release of inflammatory cytokines and chemokines. Cblb controls the association between TLR4 and the intracellular adaptor MyD88. Expression of wild-type Cblb, but not expression of a Cblb mutant that lacks E3 ubiquitin ligase function, prevents the activity of a reporter gene for the transcription factor nuclear factor-kappaB (NF-kappaB) in monocytes that have been challenged with LPS. The downregulation of TLR4 expression on the cell surface of neutrophils is impaired in the absence of Cblb. Our data reveal that Cblb regulates the TLR4-mediated acute inflammatory response that is induced by sepsis.

E3 ubiquitin ligase Cblb regulates the acute inflammatory response underlying lung injury. Publishing Authors By Initials

K Bachmaier,S Toya,X Gao,T Triantafillou,S Garrean,GY Park,RS Frey,S Vogel,R Minshall,JW Christman,C Tiruppathi,AB Malik,

For similar proteins: membrane proteins: receptors, cell surface: receptors, immunologic: receptors, pattern recognition: toll-like receptors: toll-like receptor 4 research abstracts see: proteins: membrane proteins: receptors, cell surface: receptors, immunologic: receptors, pattern recognition: toll-like receptors: toll-like receptor 4 research

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E3 ubiquitin ligase Cblb regulates the acute inflammatory response underlying lung injury. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Nature medicine

VOLUME: 13

Page Numbers: 920-6

Journal Abbreviation: Nat. Med.

ISSN: 1078-8956

DAY: 8

MONTH: 07

YEAR: 2007

E3 ubiquitin ligase Cblb regulates the acute inflammatory response underlying lung injury. Information

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LANGUAGE: eng

NlmUniqueID: 9502015

E3 ubiquitin ligase Cblb regulates the acute inflammatory response underlying lung injury. Keywords Mesh Terms:

KEYWORDS: Toll-Like Receptor 4

MESH TERMS: metabolism

Chemical & Substance for Abstract: E3 ubiquitin ligase Cblb regulates the acute inflammatory response underlying lung injury. Information

Substance Name: Cblb protein, mouse

Registry Number: EC 6.3.2.19

Grant and Affiliation Information for E3 ubiquitin ligase Cblb regulates the acute inflammatory response underlying lung injury.

AFFILIATION: Department of Pharmacology, College of Medicine, University of Illinois, E403, Medical Science Building, M/C 868, 835 S. Wolcott Avenue, Chicago, Illinois 60612, USA. kbachmai@uic.edu

Country: United States

AGENCY: United States NHLBI

GRANT: T32 HL 07829

ACRONYM: HL

MEDLINETA: Nat Med

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