SIRT1-related inhibition of pro-inflammatory responses and oxidative stress are involved in the mechanism of nonspecific low back pain relief after exercise through modulation of Toll-like receptor 4

J Biochem. 2015 Oct;158(4):299-308. doi: 10.1093/jb/mvv041. Epub 2015 Apr 27.

Abstract

Low back pain is a common clinical problem that causes disability and impaired quality of life. While the reason behind low back pain was largely considered to be of musculoskeletal origin, the contribution of inflammatory cytokines and oxidative stress could never be overlooked. Exercise has been proven to be an effective approach to treat low back pain. However, the mechanism of the exercise effect on the inflammatory cytokines and oxidative stress is still largely unknown. In this study, we revealed that exercise intervention reduces Toll-like receptor 4 (TLR-4) pathway and enhances Sirtuin 1 (SIRT1) expression in low back pain patients. We also confirmed that exercise up-regulates the expression of peroxisome proliferator-activated receptor-gamma, PPAR-γ coactivator-1 and FoxOs family proteins and also increases the activity of catalase and superoxide dismutase in patients with low back pain. Furthermore, we found that exercise intervention attenuates the oxidative stress, pro-inflammatory cytokine concentrations and p53 expression in patients with low back pain. This study demonstrates that exercise intervention improves low back pain symptoms through regulation of the SIRT1 axis with repression of oxidative stress and TLR-4 inhibition.

Keywords: SIRT1; exercise; genes; low back pain; toll like receptor 4.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cross-Sectional Studies
  • Cytokines / blood
  • Cytokines / metabolism
  • Female
  • Forkhead Box Protein O1
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation*
  • Humans
  • Low Back Pain / blood
  • Low Back Pain / immunology
  • Low Back Pain / metabolism
  • Low Back Pain / therapy*
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Male
  • Middle Aged
  • Muscle Stretching Exercises*
  • Oxidative Stress*
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Pain Measurement
  • Resistance Training*
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism*
  • Taiwan
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Cytokines
  • FOXO1 protein, human
  • FOXO3 protein, human
  • Forkhead Box Protein O1
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors
  • PPAR gamma
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • SIRT1 protein, human
  • Sirtuin 1