Role of NF-κB transcription factors in antiinflammatory and proinflammatory actions of mechanical signals

Sudha Agarwal, James Deschner, Ping Long, Anupam Verma, Cynthia Hofman, Christopher H. Evans, Nicholas Piesco

Research output: Contribution to journalArticle

121 Scopus citations

Abstract

Objective. The mechanisms by which chondrocytes convert biomechanical signals into intracellular biochemical events are not well understood. In this study, we sought to determine the intracellular mechanisms of the magnitude-dependent actions of mechanical signals. Methods. Chondrocytes isolated from rabbit articular cartilage were grown on flexible membranes. Cells were subjected to cyclic tensile strain (CTS) of various magnitudes in the presence or absence of interleukin-1β (IL-1β), which was used as a proinflammatory signal for designated time intervals. The regulation of NF-κB was measured by reverse transcriptase-polymerase chain reaction, electrophoretic mobility shift assay, and immunofluorescence. Results. CTS of low magnitudes (4-8% equibiaxial strain) was a potent inhibitor of IL-1β-dependent NF-κB nuclear translocation. Cytoplasmic retention of NF-κB and reduction of its synthesis led to sustained suppression of proinflammatory gene induction. In contrast, proinflammatory signals generated by CTS of high magnitudes (15-18% equibiaxial strain) mimicked the actions of IL-1β and induced rapid nuclear translocation of NF-κB subunits p65 and p50. Conclusion. Magnitude-dependent signals of mechanical strain utilize the NF-κB transcription factors as common elements to abrogate or aggravate proinflammatory responses. Furthermore, the intracellular events induced by mechanical overload are similar to those that are initiated by proinflammatory cytokines in arthritis.

Original languageEnglish (US)
Pages (from-to)3541-3548
Number of pages8
JournalArthritis and rheumatism
Volume50
Issue number11
DOIs
StatePublished - Nov 1 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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