• Home
  • Search Results
  • Transcriptome assessment reveals a dominant role for TLR4 in the activation of human monocytes by the alarmin MRP8.

Transcriptome assessment reveals a dominant role for TLR4 in the activation of human monocytes by the alarmin MRP8.

Journal of immunology (Baltimore, Md. : 1950) (2014-12-17)
Selina K Fassl, Judith Austermann, Olympia Papantonopoulou, Mona Riemenschneider, Jia Xue, Damien Bertheloot, Nicole Freise, Christoph Spiekermann, Anika Witten, Dorothee Viemann, Susanne Kirschnek, Monika Stoll, Eicke Latz, Joachim L Schultze, Johannes Roth, Thomas Vogl
ABSTRACT

The alarmins myeloid-related protein (MRP)8 and MRP14 are the most prevalent cytoplasmic proteins in phagocytes. When released from activated or necrotic phagocytes, extracellular MRP8/MRP14 promote inflammation in many diseases, including infections, allergies, autoimmune diseases, rheumatoid arthritis, and inflammatory bowel disease. The involvement of TLR4 and the multiligand receptor for advanced glycation end products as receptors during MRP8-mediated effects on inflammation remains controversial. By comparative bioinformatic analysis of genome-wide response patterns of human monocytes to MRP8, endotoxins, and various cytokines, we have developed a model in which TLR4 is the dominant receptor for MRP8-mediated phagocyte activation. The relevance of the TLR4 signaling pathway was experimentally validated using human and murine models of TLR4- and receptor for advanced glycation end products-dependent signaling. Furthermore, our systems biology approach has uncovered an antiapoptotic role for MRP8 in monocytes, which was corroborated by independent functional experiments. Our data confirm the primary importance of the TLR4/MRP8 axis in the activation of human monocytes, representing a novel and attractive target for modulation of the overwhelming innate immune response.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Perchloric acid, ACS reagent, 70%
Sigma-Aldrich
Propidium iodide, ≥94.0% (HPLC)
Sigma-Aldrich
Propidium iodide solution, solution (1.0 mg/ml in water)
Sigma-Aldrich
Perchloric acid, 70%, 99.999% trace metals basis
Sigma-Aldrich
GeneJuice® Transfection Reagent, Non-lipid based chemical transfection reagent optimized for maximum transfection efficiency, ease-of-use, and minimal cytotoxicity on a wide variety of mammallian cells.
Sigma-Aldrich
Perchloric acid, ACS reagent, 60%
Sigma-Aldrich
Propidium iodide, ≥94% (HPLC)
Sigma-Aldrich
Estradiol, meets USP testing specifications
Sigma-Aldrich
Perchloric acid, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., 70.0-72.0%
Supelco
Estradiol, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
1,2,4,5-Tetramethylbenzene, 98%
Supelco
1,2,4,5-Tetramethylbenzene, Standard for quantitative NMR, TraceCERT®
Supelco
Perchloric acid concentrate, 0.01 M HClO4 in water (0.01N), eluent concentrate for IC
Supelco
Staurosporine, VETRANAL®, analytical standard
USP
Estradiol, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Perchloric acid, puriss. p.a., ACS reagent, packed in coated, shock- and leak-protected glass bottle, ≥60% (T)
Sigma-Aldrich
DL-p-Chloroamphetamine hydrochloride, ≥94% (HPLC)