Myeloid differentiation protein 2 silencing decreases LPS-induced cytokine production and TLR4/MyD88 pathway activity in alveolar macrophages.

Abstract

Lipopolysaccharides (LPSs) activate the innate immune response during Gram-negative bacterial infections through the Toll-like receptor 4 (TLR4)/myeloid differentiation protein 2 (MD-2) complex. MD-2 binds LPS with high affinity and is critical for TLR4-dependent signal transduction. However, the exact role of MD-2 on LPS signal transduction and cytokine production in alveolar macrophages (AMs) remains unclear. This study showed that the transcription levels of MD-2, TLR4 and MyD88 in the NR8383 cell line were up-regulated after LPS stimulation and that the increased transcript levels were attenuated after RNA interference of MD-2. Similarly, LPS induced increases in TNF-α, IL-1β and IL-6 protein levels in NR8383 cell supernatants was significantly inhibited by MD-2 silencing. These results suggest that in association with the TLR4/MyD88 signaling pathway LPS-induced cytokine production can be partially reduced by MD-2 silencing in the rat pulmonary alveolar macrophage cell line NR8383. MD-2 silencing was proved to be a useful tool for testing the role of MD-2 in the LPS signaling pathway and may be a potential therapeutic tool against LPS-induced lung inflammation.

• Authors: Weiying Ren, Lijuan Hu, Feng Hua, Jianjun Jin, Yanying Wang, Lei Zhu
• Journal: Immunology letters (Immunol Lett) Vol. 141 Issue 1 Pg. 94-101 (Dec 30 2011) ISSN: 1879-0542 [Electronic] Netherlands
• PMID: 21849156 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Interleukin-1beta
• Interleukin-6
• Lipopolysaccharides
• Lymphocyte Antigen 96
• Myd88 protein, rat
• Myeloid Differentiation Factor 88
• RNA, Small Interfering
• Tlr4 protein, rat
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Cell Line
• Interleukin-1beta (analysis, antagonists & inhibitors)
• Interleukin-6 (analysis, antagonists & inhibitors)
• Lipopolysaccharides (pharmacology)
• Lymphocyte Antigen 96 (antagonists & inhibitors, genetics, metabolism)
• Macrophages, Alveolar (immunology, metabolism)
• Myeloid Differentiation Factor 88 (genetics, metabolism)
• Pneumonia (therapy)
• RNA, Small Interfering (pharmacology)
• Rats
• Signal Transduction (drug effects, immunology)
• Toll-Like Receptor 4 (genetics, metabolism)
• Tumor Necrosis Factor-alpha (analysis, antagonists & inhibitors)