Bruton's tyrosine kinase is required for TLR-induced IL-10 production.

Bruton's tyrosine kinase is required for TLR-induced IL-10 production. Research Abstract Details 

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Bruton's tyrosine kinase is required for TLR-induced IL-10 production. Abstract Text:

Nathan W Schmidt,Vivian T Thieu,Brandon A Mann,Ayele-Nati N Ahyi,Mark H Kaplan,

Bruton's tyrosine kinase (Btk) is a critical signaling mediator downstream of the B cell Ag receptor. X-linked agammaglobulinemia is caused by mutations in Btk resulting in multiple defects in B cell development and function, and recurrent bacterial infections. Recent evidence has also supported a role for Btk in TLR signaling. We demonstrate that Btk is activated by TLR4 in primary macrophages and is required for normal TLR-induced IL-10 production in multiple macrophage populations. Btk-deficient bone marrow-derived macrophages secrete decreased levels of IL-10 in response to multiple TLR ligands, compared with wild-type (WT) cells. Similarly, Btk-deficient peritoneal and splenic macrophages secrete decreased IL-10 levels compared with WT cultures. This phenotype correlates with Btk-dependent induction of NF-kappaB and AP-1 DNA binding activity, and altered commensal bacteria populations. Decreased IL-10 production may be responsible for increased IL-6 because blocking IL-10 in WT cultures increased IL-6 production, and supplementation of IL-10 to Btk-deficient cultures decreased IL-6 production. Similarly, injection of IL-10 in vivo with LPS decreases the elevated IL-6 serum levels during endotoxemia in Btk-deficient mice. These data further support a role for Btk in regulating TLR-induced cytokine production from APCs and provide downstream targets for analysis of Btk function.

Bruton's tyrosine kinase is required for TLR-induced IL-10 production. Publishing Authors By Initials

NW Schmidt,VT Thieu,BA Mann,AN Ahyi,MH Kaplan,

For similar genetic processes: gene expression regulation: up-regulation research abstracts see: genetic processes: gene expression regulation: up-regulation research

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Bruton's tyrosine kinase is required for TLR-induced IL-10 production. Journal Published:

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

Journal: Journal of immunology (Baltimore, Md. : 1950)

VOLUME: 177

Page Numbers: 7203-10

Journal Abbreviation: J. Immunol.

ISSN: 0022-1767

DAY: 15

MONTH: Nov

YEAR: 2006

Bruton's tyrosine kinase is required for TLR-induced IL-10 production. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985117

Bruton's tyrosine kinase is required for TLR-induced IL-10 production. Keywords Mesh Terms:

KEYWORDS: Up-Regulation

MESH TERMS: immunology

Chemical & Substance for Abstract: Bruton's tyrosine kinase is required for TLR-induced IL-10 production. Information

Substance Name: Protein-Tyrosine Kinases

Registry Number: EC 2.7.1.112

Grant and Affiliation Information for Bruton's tyrosine kinase is required for TLR-induced IL-10 production.

AFFILIATION: Department of Pediatrics, H. B. Wells Center for Pediatric Research and Walther Oncology Center, Indiana University School of Medicine, and Walther Cancer Institute, Indianapolis, IN 46202, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL007910

ACRONYM: HL

MEDLINETA: J Immunol

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