RNA interference inhibits high mobility group box 1 by lipopolysaccharide- activated murine macrophage RAW 264.7 secretion

Han Chung Hu, Ting Ya Wang, Yung Che Chen, Chin Chou Wang, Meng-Chih Lin*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

3 Scopus citations

Abstract

Background: This study aims to evaluate the influence of RNA interference (RNAi) on the high mobility group box 1 (HMGB-1) in the lipopolysaccharide (LPS)-induced murine macrophage cell line RAW 264.7. Materials and Methods: In order to observe the effect of RNAi on HMGB-1, tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and transforming growth factor β (TGF-β) levels, the RAW 264.7 cell line was divided into five treatment groups to measure separately as a function of time of negative control, LPS stimulation only, LPS + HMGB-1 short interfering RNAs (siRNAs), LPS + negative control siRNAs (siNC), and LPS + nafamostat mesilate (NM). Results: Measurement does show HMGB-1 expression in the LPS-activated macrophages in an explicit time-dependent manner. The HMGB-1 cellular level is consistently knocked down 80%∼85% by the siRNA; TNF-α, IL-6, and TGF-β levels in turn significantly decrease following siRNA delivery to the inflammatory response. HMGB-1 expression is lower in the LPS + NM group than the LPS + HMGB-1 siRNA group at the initial stage, however, a significantly lower level of HMGB-1 in the siRNA group is observed 48 h later. The decrease of TNF-α, IL-6, and TGF-β levels in the LPS-induced inflammatory response is also observed in both groups. Conclusions: Our results demonstrate that HMGB-1 RNAi treatment of LPS-stimulated macrophages inhibit HMGB-1 and remarkably reduce the LPS-induced inflammatory responses. Hence, RNAi is highly recommended as a potential candidate for a new therapeutic strategy to minimize or, to a lesser extent, prevent the LPS-induced inflammatory injury.

Original languageEnglish
Pages (from-to)e181-e187
JournalJournal of Surgical Research
Volume168
Issue number2
DOIs
StatePublished - 15 06 2011
Externally publishedYes

Keywords

  • (TNF-α)
  • high mobility group box 1 (HMGB-1)
  • interleukin-6 (IL-6)
  • short interfering RNAs (siRNAs)
  • transforming growth factor β (TGF-β)
  • tumor necrosis factor α

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