The functional variant (Asp299gly) of toll-like receptor 4 (TLR4) influences TLR4-mediated cytokine production in rheumatoid arthritis

Mieke F Roelofs; Mark H Wenink; Erik J M Toonen; Marieke J H Coenen; Leo A B Joosten; Wim B van den Berg; Piet L C M van Riel; Timothy R D J Radstake

The functional variant (Asp299gly) of toll-like receptor 4 (TLR4) influences TLR4-mediated cytokine production in rheumatoid arthritis

Mieke F Roelofs, Mark H Wenink, Erik J M Toonen, Marieke J H Coenen, Leo A B Joosten, Wim B van den Berg, Piet L C M van Riel, Timothy R D J Radstake

Rheumatology & Clinical Immunology

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

OBJECTIVE: To investigate functional consequences of the Toll-like receptor 4 (TLR4) variant (Asp299Gly) in rheumatoid arthritis (RA).

METHODS: Peripheral blood mononuclear cells from 28 patients with RA carrying or not carrying the TLR4 variant were incubated with lipopolysaccharide (LPS) and heat shock protein B8 (HSPB8). Concentrations of interleukin 6 (IL-6), tumor necrosis factor-alpha(TNF-alpha), and IL-10 were determined along with TLR4 and CD14 expression.

RESULTS: TLR4 expression was similar in patients carrying or not carrying the variant. In contrast, both LPS and HSPB8 resulted in significantly lower secretion of IL-6, TNF-alpha, and IL-10 in those who carried the variant, whereas the frequency of CD14+ cells was higher in these individuals.

CONCLUSION: TLR4 variant clearly reduces its potency to mediate signaling. Correction for CD14+ cells is necessary in comparable experiments.

Original language	English
Pages (from-to)	558-61
Number of pages	4
Journal	Journal of Rheumatology
Volume	35
Issue number	4
Publication status	Published - Apr 2008

Keywords

Aged
Arthritis, Rheumatoid
Cytokines
Female
Gene Expression Regulation
Heat-Shock Proteins
Humans
Leukocytes, Mononuclear
Lipopolysaccharides
Male
Middle Aged
Mutation, Missense
Protein-Serine-Threonine Kinases
Signal Transduction
Toll-Like Receptor 4
Journal Article
Research Support, Non-U.S. Gov't

Cite this

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title = "The functional variant (Asp299gly) of toll-like receptor 4 (TLR4) influences TLR4-mediated cytokine production in rheumatoid arthritis",

abstract = "OBJECTIVE: To investigate functional consequences of the Toll-like receptor 4 (TLR4) variant (Asp299Gly) in rheumatoid arthritis (RA).METHODS: Peripheral blood mononuclear cells from 28 patients with RA carrying or not carrying the TLR4 variant were incubated with lipopolysaccharide (LPS) and heat shock protein B8 (HSPB8). Concentrations of interleukin 6 (IL-6), tumor necrosis factor-alpha(TNF-alpha), and IL-10 were determined along with TLR4 and CD14 expression.RESULTS: TLR4 expression was similar in patients carrying or not carrying the variant. In contrast, both LPS and HSPB8 resulted in significantly lower secretion of IL-6, TNF-alpha, and IL-10 in those who carried the variant, whereas the frequency of CD14+ cells was higher in these individuals.CONCLUSION: TLR4 variant clearly reduces its potency to mediate signaling. Correction for CD14+ cells is necessary in comparable experiments.",

keywords = "Aged, Arthritis, Rheumatoid, Cytokines, Female, Gene Expression Regulation, Heat-Shock Proteins, Humans, Leukocytes, Mononuclear, Lipopolysaccharides, Male, Middle Aged, Mutation, Missense, Protein-Serine-Threonine Kinases, Signal Transduction, Toll-Like Receptor 4, Journal Article, Research Support, Non-U.S. Gov't",

author = "Roelofs, {Mieke F} and Wenink, {Mark H} and Toonen, {Erik J M} and Coenen, {Marieke J H} and Joosten, {Leo A B} and {van den Berg}, {Wim B} and {van Riel}, {Piet L C M} and Radstake, {Timothy R D J}",

year = "2008",

month = apr,

language = "English",

volume = "35",

pages = "558--61",

journal = "Journal of Rheumatology",

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TY - JOUR

T1 - The functional variant (Asp299gly) of toll-like receptor 4 (TLR4) influences TLR4-mediated cytokine production in rheumatoid arthritis

AU - Roelofs, Mieke F

AU - Wenink, Mark H

AU - Toonen, Erik J M

AU - Coenen, Marieke J H

AU - Joosten, Leo A B

AU - van den Berg, Wim B

AU - van Riel, Piet L C M

AU - Radstake, Timothy R D J

PY - 2008/4

Y1 - 2008/4

N2 - OBJECTIVE: To investigate functional consequences of the Toll-like receptor 4 (TLR4) variant (Asp299Gly) in rheumatoid arthritis (RA).METHODS: Peripheral blood mononuclear cells from 28 patients with RA carrying or not carrying the TLR4 variant were incubated with lipopolysaccharide (LPS) and heat shock protein B8 (HSPB8). Concentrations of interleukin 6 (IL-6), tumor necrosis factor-alpha(TNF-alpha), and IL-10 were determined along with TLR4 and CD14 expression.RESULTS: TLR4 expression was similar in patients carrying or not carrying the variant. In contrast, both LPS and HSPB8 resulted in significantly lower secretion of IL-6, TNF-alpha, and IL-10 in those who carried the variant, whereas the frequency of CD14+ cells was higher in these individuals.CONCLUSION: TLR4 variant clearly reduces its potency to mediate signaling. Correction for CD14+ cells is necessary in comparable experiments.

AB - OBJECTIVE: To investigate functional consequences of the Toll-like receptor 4 (TLR4) variant (Asp299Gly) in rheumatoid arthritis (RA).METHODS: Peripheral blood mononuclear cells from 28 patients with RA carrying or not carrying the TLR4 variant were incubated with lipopolysaccharide (LPS) and heat shock protein B8 (HSPB8). Concentrations of interleukin 6 (IL-6), tumor necrosis factor-alpha(TNF-alpha), and IL-10 were determined along with TLR4 and CD14 expression.RESULTS: TLR4 expression was similar in patients carrying or not carrying the variant. In contrast, both LPS and HSPB8 resulted in significantly lower secretion of IL-6, TNF-alpha, and IL-10 in those who carried the variant, whereas the frequency of CD14+ cells was higher in these individuals.CONCLUSION: TLR4 variant clearly reduces its potency to mediate signaling. Correction for CD14+ cells is necessary in comparable experiments.

KW - Aged

KW - Arthritis, Rheumatoid

KW - Cytokines

KW - Female

KW - Gene Expression Regulation

KW - Heat-Shock Proteins

KW - Humans

KW - Leukocytes, Mononuclear

KW - Lipopolysaccharides

KW - Male

KW - Middle Aged

KW - Mutation, Missense

KW - Protein-Serine-Threonine Kinases

KW - Signal Transduction

KW - Toll-Like Receptor 4

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

M3 - Article

C2 - 18381796

SN - 0315-162X

VL - 35

SP - 558

EP - 561

JO - Journal of Rheumatology

JF - Journal of Rheumatology

IS - 4

ER -

The functional variant (Asp299gly) of toll-like receptor 4 (TLR4) influences TLR4-mediated cytokine production in rheumatoid arthritis

Abstract

Keywords

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