PMID- 18565769
OWN - NLM
STAT- MEDLINE
DCOM- 20090220
LR  - 20211020
IS  - 1522-9653 (Electronic)
IS  - 1063-4584 (Print)
IS  - 1063-4584 (Linking)
VI  - 16
IP  - 12
DP  - 2008 Dec
TI  - Exuberant expression of chemokine genes by adult human articular chondrocytes in 
      response to IL-1beta.
PG  - 1560-71
LID - 10.1016/j.joca.2008.04.027 [doi]
AB  - OBJECTIVE: To provide a more complete picture of the effect of interleukin-1 beta 
      (IL-1beta) on adult human articular chondrocyte gene expression, in contrast to 
      the candidate gene approach. DESIGN: Chondrocytes from human knee cartilage were 
      cultured in medium containing IL-1beta. Changes in gene expression were analyzed 
      by microarray and reverse transcriptase-polymerase chain reaction analysis. The 
      ability of transforming growth factor beta-1 (TGF-beta1), fibroblast growth 
      factor (FGF)-18, and bone morphogenetic protein 2 (BMP-2) to alter the effects of 
      IL-1beta was analyzed. Computational analysis of the promoter regions of 
      differentially expressed genes for transcription factor binding motifs was 
      performed. RESULTS: IL-1beta-treated human chondrocytes showed significant 
      increases in the expression of granulocyte colony stimulating factor-3, 
      endothelial leukocyte adhesion molecule 1 and leukemia inhibitory factor as well 
      as for a large group of chemokines that include CXCL1, CXCL2, CXCL3, CXCL5, 
      CXCL6, CXCL8, CCL2, CCL3, CCL4, CCL5, CCL8, CCL20, CCL3L1, CX3CL1 and the 
      cytokine IL-6. As expected, the mRNA for matrix metalloproteinase (MMP)-13 and 
      BMP-2 also increased while mRNA for the matrix genes COL2A1 and aggrecan was 
      down-regulated. A subset of chemokines increased rapidly at very low levels of 
      IL-1beta. The phenotype induced by IL-1beta was partially reversed by TGF-beta1, 
      but not by BMP-2. In the presence of IL-1beta, FGF-18 increased expression of 
      ADAMTS-4, aggrecan, BMP-2, COL2A1, CCL3, CCL4, CCL20, CXCL1, CXCL3, CXCL6, 
      IL-1beta, IL-6, and IL-8 and decreased ADAMTS-5, MMP-13, CCL2, and CCL8. 
      Computational analysis revealed a high likelihood that the most up-regulated 
      chemokines are regulated by the transcription factors myocyte enhancer binding 
      factor-3 (MEF-3), CCAAT/enhancer binding protein (C/EBP) and nuclear factor-kappa 
      B (NF-kappaB). CONCLUSION: IL-1beta has a diverse effect on gene expression 
      profile in human chondrocytes affecting matrix genes as well as chemokines and 
      cytokines. TGF-beta1 has the ability to antagonize some of the phenotype induced 
      by IL-1beta.
FAU - Sandell, L J
AU  - Sandell LJ
AD  - Department of Orthopaedic Surgery, Washington University School of Medicine at 
      Barnes-Jewish Hospital, St Louis, MO 63110, United States. sandelll@wustl.edu
FAU - Xing, X
AU  - Xing X
FAU - Franz, C
AU  - Franz C
FAU - Davies, S
AU  - Davies S
FAU - Chang, L-W
AU  - Chang LW
FAU - Patra, D
AU  - Patra D
LA  - eng
GR  - R01 AR05084/AR/NIAMS NIH HHS/United States
GR  - R01 AR036994-21/AR/NIAMS NIH HHS/United States
GR  - R01 AR036994-23/AR/NIAMS NIH HHS/United States
GR  - R01 AR036994/AR/NIAMS NIH HHS/United States
GR  - R01 AR036994-22/AR/NIAMS NIH HHS/United States
GR  - R01 AR050847-02/AR/NIAMS NIH HHS/United States
GR  - R01 AR050847-05/AR/NIAMS NIH HHS/United States
GR  - R01 AR045550/AR/NIAMS NIH HHS/United States
GR  - R01 AR045550-10/AR/NIAMS NIH HHS/United States
GR  - R01 AR050847/AR/NIAMS NIH HHS/United States
GR  - R01 AR050847-03/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080618
PL  - England
TA  - Osteoarthritis Cartilage
JT  - Osteoarthritis and cartilage
JID - 9305697
RN  - 0 (Chemokines)
RN  - 0 (Interleukin-1beta)
RN  - 0 (NF-kappa B)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (fibroblast growth factor 18)
RN  - 62031-54-3 (Fibroblast Growth Factors)
SB  - IM
MH  - Arthritis/genetics/*metabolism
MH  - Cartilage, Articular/*metabolism
MH  - Cells, Cultured
MH  - Chemokines/metabolism/pharmacology
MH  - Chondrocytes/*metabolism
MH  - Fibroblast Growth Factors/*antagonists & inhibitors
MH  - Gene Expression Regulation/genetics
MH  - Humans
MH  - Interleukin-1beta/*antagonists & inhibitors/pharmacology
MH  - NF-kappa B/metabolism
MH  - Transforming Growth Factor beta/*antagonists & inhibitors/pharmacology
MH  - Up-Regulation
PMC - PMC2605974
MID - NIHMS80853
EDAT- 2008/06/21 09:00
MHDA- 2009/02/21 09:00
PMCR- 2009/12/01
CRDT- 2008/06/21 09:00
PHST- 2008/02/07 00:00 [received]
PHST- 2008/04/27 00:00 [accepted]
PHST- 2008/06/21 09:00 [pubmed]
PHST- 2009/02/21 09:00 [medline]
PHST- 2008/06/21 09:00 [entrez]
PHST- 2009/12/01 00:00 [pmc-release]
AID - S1063-4584(08)00144-1 [pii]
AID - 10.1016/j.joca.2008.04.027 [doi]
PST - ppublish
SO  - Osteoarthritis Cartilage. 2008 Dec;16(12):1560-71. doi: 
      10.1016/j.joca.2008.04.027. Epub 2008 Jun 18.