Luteolin inhibits inflammatory responses via p38/MK2/TTP-mediated mRNA stability

Molecules. 2013 Jul 9;18(7):8083-94. doi: 10.3390/molecules18078083.

Abstract

Luteolin (Lut) is a common dietary flavonoid present in Chinese herbal medicines that has been reported to have important anti-inflammatory properties. The purposes of this study were to observe the inhibition of lipopolysaccharide (LPS)-induced inflammatory responses in bone marrow macrophages (BMM) by Lut, and to examine whether this inhibition involves p38/MK2/TTP-mediated mRNA stability. Lut suppressed the production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in a dose-dependent manner according to enzyme-linked immunosorbent assay (ELISA) analysis. Lut also shortened the half-lives of the TNF-α and IL-6 mRNAs according to real-time PCR analysis. Western blots were performed to assess the activation of p38 and MK2 as well as the expression of TTP. The results indicated that Lut inhibited p38 and MK2 phosphorylation while promoting TTP expression. These results suggest that the anti-inflammatory effects of Lut are partially mediated through p38/MK2/TTP-regulated mRNA stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / metabolism
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Drugs, Chinese Herbal / metabolism
  • Drugs, Chinese Herbal / pharmacology
  • Enzyme Activation / drug effects
  • Female
  • Femur
  • Interleukin-6 / biosynthesis
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Luteolin / chemistry
  • Luteolin / pharmacology*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Phosphorylation / drug effects
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA Stability / drug effects
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Tibia
  • Tristetraprolin / biosynthesis*
  • Tristetraprolin / genetics
  • Tumor Necrosis Factor-alpha / biosynthesis
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Drugs, Chinese Herbal
  • Interleukin-6
  • Intracellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Tristetraprolin
  • Tumor Necrosis Factor-alpha
  • MAP-kinase-activated kinase 2
  • Protein Serine-Threonine Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Luteolin