PMID- 21276216
OWN - NLM
STAT- MEDLINE
DCOM- 20120210
LR  - 20220410
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 13
IP  - 1
DP  - 2011 Jan 28
TI  - The involvement of interleukin-1 and interleukin-4 in the response of human 
      annulus fibrosus cells to cyclic tensile strain: an altered mechanotransduction 
      pathway with degeneration.
PG  - R8
LID - 10.1186/ar3229 [doi]
AB  - INTRODUCTION: Recent evidence suggests that intervertebral disc (IVD) cells 
      derived from degenerative tissue are unable to respond to physiologically 
      relevant mechanical stimuli in the 'normal' anabolic manner, but instead respond 
      by increasing matrix catabolism. Understanding the nature of the biological 
      processes which allow disc cells to sense and respond to mechanical stimuli (a 
      process termed 'mechanotransduction') is important to ascertain whether these 
      signalling pathways differ with disease. The aim here was to investigate the 
      involvement of interleukin (IL)-1 and IL-4 in the response of annulus fibrosus 
      (AF) cells derived from nondegenerative and degenerative tissue to cyclic tensile 
      strain to determine whether cytokine involvement differed with IVD degeneration. 
      METHODS: AF cells were isolated from nondegenerative and degenerative human IVDs, 
      expanded in monolayers and cyclically strained in the presence or absence of the 
      cytokine inhibitors IL-1 receptor antagonist (IL-1Ra) or IL-4 receptor antibody 
      (IL-4RAb) with 10% strain at 1.0 Hz for 20 minutes using a Flexcell strain 
      device. Total RNA was extracted from the cells at time points of baseline control 
      and 1 or 24 hours poststimulation. Quantitative real-time polymerase chain 
      reaction was used to analyse the gene expression of matrix proteins (aggrecan and 
      type I collagen) and enzymes (matrix metalloproteinase 3 (MMP3) and a disintegrin 
      and metalloproteinase with a thrombospondin type 1 motif 4 (ADAMTS4)). RESULTS: 
      Expression of catabolic genes (MMP3 and ADAMTS4) decreased in AF cells derived 
      from nondegenerative tissue in response to 1.0-Hz stimulation, and this decrease 
      in gene expression was inhibited or increased following pretreatment of cells 
      with IL-1Ra or IL-4RAb respectively. Treatment of AF cells derived from 
      degenerative tissue with an identical stimulus (1.0-Hz) resulted in reduced 
      anabolic gene expression (aggrecan and type I collagen), with IL-1Ra or IL-4RAb 
      pretreatment having no effect. CONCLUSIONS: Both IL-1 and IL-4 are involved in 
      the response of AF cells derived from nondegenerative tissue to 1.0-Hz cyclic 
      tensile strain. Interestingly, the altered response observed at 1.0-Hz in AF 
      cells from degenerative tissue appears to be independent of either cytokine, 
      suggesting an alternative mechanotransduction pathway in operation.
FAU - Gilbert, Hamish T J
AU  - Gilbert HT
AD  - School of Biomedicine, Faculty of Medical and Human Sciences, University of 
      Manchester, Manchester M139PL, UK.
FAU - Hoyland, Judith A
AU  - Hoyland JA
FAU - Freemont, Anthony J
AU  - Freemont AJ
FAU - Millward-Sadler, Sarah J
AU  - Millward-Sadler SJ
LA  - eng
GR  - 17850/Arthritis Research UK/United Kingdom
GR  - Department of Health/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110128
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (IL4 protein, human)
RN  - 0 (Interleukin-1)
RN  - 207137-56-2 (Interleukin-4)
SB  - IM
MH  - Adult
MH  - Cells, Cultured
MH  - Gene Expression
MH  - Gene Expression Regulation/*physiology
MH  - Humans
MH  - Immunohistochemistry
MH  - Interleukin-1/*biosynthesis
MH  - Interleukin-4/*biosynthesis
MH  - Intervertebral Disc/*metabolism
MH  - Intervertebral Disc Degeneration/*metabolism
MH  - Mechanotransduction, Cellular/*physiology
MH  - Middle Aged
MH  - Real-Time Polymerase Chain Reaction
MH  - Stress, Mechanical
PMC - PMC3241352
EDAT- 2011/02/01 06:00
MHDA- 2012/02/11 06:00
PMCR- 2011/01/28
CRDT- 2011/02/01 06:00
PHST- 2010/09/06 00:00 [received]
PHST- 2010/12/01 00:00 [revised]
PHST- 2011/01/28 00:00 [accepted]
PHST- 2011/02/01 06:00 [entrez]
PHST- 2011/02/01 06:00 [pubmed]
PHST- 2012/02/11 06:00 [medline]
PHST- 2011/01/28 00:00 [pmc-release]
AID - ar3229 [pii]
AID - 10.1186/ar3229 [doi]
PST - epublish
SO  - Arthritis Res Ther. 2011 Jan 28;13(1):R8. doi: 10.1186/ar3229.