Role of NF-kappaB transcription factors in antiinflammatory and proinflammatory actions of mechanical signals
Language: 
English
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-1beta (IL-1beta), which was used as a proinflammatory signal for designated time intervals. The regulation of NF-kappaB 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-1beta-dependent NF-kappaB nuclear translocation. Cytoplasmic retention of NF-kappaB 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-1beta and induced rapid nuclear translocation of NF-kappaB subunits p65 and p50. CONCLUSION: Magnitude-dependent signals of mechanical strain utilize the NF-kappaB 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.

Author(s): 
Agarwal, Sudha
Deschner, James
Long, Ping
Verma, Anupam
Hofman, Cynthia
Evans, Christopher H.
Piesco, Nicholas
Item Type: 
Journal Article
Publication Title: 
Arthritis and Rheumatism
Journal Abbreviation: 
Arthritis Rheum.
Publication Date: 
Nov 2004
Publication Year: 
2004
Pages: 
3541-3548
Volume: 
50
Issue: 
11
ISSN: 
0004-3591
DOI: 
10.1002/art.20601
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 15529376

Turabian/Chicago Citation

Sudha Agarwal, James Deschner, Ping Long, Anupam Verma, Cynthia Hofman, Christopher H. Evans and Nicholas Piesco. Nov 2004. "Role of NF-kappaB transcription factors in antiinflammatory and proinflammatory actions of mechanical signals." Arthritis and Rheumatism 50: 11: 3541-3548. 10.1002/art.20601.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1002/art.20601 | issn = 0004-3591 | volume = 50 | pages = 3541-3548 | last = Agarwal | first = Sudha | coauthors = Deschner, James, Long, Ping, Verma, Anupam, Hofman, Cynthia, Evans, Christopher H., Piesco, Nicholas | title = Role of NF-kappaB transcription factors in antiinflammatory and proinflammatory actions of mechanical signals | journal = Arthritis and Rheumatism | date = Nov 2004 | pmid = | pmc = }} </ref>