PMID- 1365641
OWN - NLM
STAT- MEDLINE
DCOM- 19920909
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 90
IP  - 2
DP  - 1992 Aug
TI  - Monocyte chemoattractant protein-1 (MCP-1) expression in human articular 
      cartilage. Induction by peptide regulatory factors and differential effects of 
      dexamethasone and retinoic acid.
PG  - 488-96
AB  - Monocyte influx and activation in synovial joints are important in the 
      pathogenesis of both degenerative and inflammatory arthropathies. In this study, 
      we demonstrate the potential of articular cartilage to directly modulate these 
      events. IL-1-stimulated human articular chondrocytes transcribed 0.7-kb monocyte 
      chemoattractant protein-1 (MCP-1) mRNA. In situ hybridization of cartilage organ 
      cultures revealed MCP-1 transcripts in chondrocytes in the superficial tangential 
      zone within 2 h of stimulation with IL-1. Chondrocytes in deeper layers responded 
      by 4 h and reached maximum MCP-1 mRNA levels by 8-12 h. IL-1-stimulated cartilage 
      organ and chondrocyte monolayer cultures released functional monocyte chemotactic 
      activity. This was neutralized by a monoclonal antibody specific for MCP-1, and 
      was associated with the synthesis and secretion of immunoreactive 13-kD and 15-kD 
      isoforms of MCP-1. Regulators and signal transduction pathways involved with the 
      expression of the MCP-1 gene in chondrocytes were analyzed. Steady-state mRNA 
      levels were increased by the known chondrocyte activators IL-1, tumor necrosis 
      factor alpha, LPS, platelet-derived growth factor, and transforming growth factor 
      beta. In addition, leukemia inhibitory factor induced MCP-1 gene expression and 
      protein synthesis, identifying this cytokine as a new regulator of chondrocyte 
      function. Dexamethasone blunted the induction of MCP-1 gene expression by IL-1 
      and by activators of protein kinase A as well as protein kinase C signal 
      transduction pathways. In contrast, retinoic acid strongly increased phorbol 
      myristate acetate-induced MCP-1 expression and potentiated the effects of IL-1 
      and LPS. In conclusion, chondrocytes express MCP-1 in response to factors that 
      are present in cartilage or synovium. This provides a mechanism by which 
      cartilage can play an active role in the initiation and progression of arthritis.
FAU - Villiger, P M
AU  - Villiger PM
AD  - Sam and Rose Stein Institute for Research on Aging, University of California, San 
      Diego, La Jolla 92093.
FAU - Terkeltaub, R
AU  - Terkeltaub R
FAU - Lotz, M
AU  - Lotz M
LA  - eng
GR  - AG-00776/AG/NIA NIH HHS/United States
GR  - AR-39799/AR/NIAMS NIH HHS/United States
GR  - DK-36702/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemotactic Factors)
RN  - 0 (Growth Inhibitors)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-6)
RN  - 0 (LIF protein, human)
RN  - 0 (Leukemia Inhibitory Factor)
RN  - 0 (Lymphokines)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor beta)
RN  - 5688UTC01R (Tretinoin)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Base Sequence
MH  - Cartilage, Articular/*physiology
MH  - Chemokine CCL2
MH  - Chemotactic Factors/*biosynthesis/chemistry/genetics
MH  - Dexamethasone/*pharmacology
MH  - Gene Expression/drug effects
MH  - Growth Inhibitors/pharmacology
MH  - Humans
MH  - Interleukin-1/pharmacology
MH  - *Interleukin-6
MH  - Leukemia Inhibitory Factor
MH  - Lymphokines/pharmacology
MH  - Molecular Sequence Data
MH  - Molecular Weight
MH  - Nucleic Acid Hybridization
MH  - Oligodeoxyribonucleotides/chemistry
MH  - Organ Culture Techniques
MH  - RNA, Messenger/genetics
MH  - Transforming Growth Factor beta/pharmacology
MH  - Tretinoin/*pharmacology
PMC - PMC443125
EDAT- 1992/08/01 00:00
MHDA- 1992/08/01 00:01
PMCR- 1992/08/01
CRDT- 1992/08/01 00:00
PHST- 1992/08/01 00:00 [pubmed]
PHST- 1992/08/01 00:01 [medline]
PHST- 1992/08/01 00:00 [entrez]
PHST- 1992/08/01 00:00 [pmc-release]
AID - 10.1172/JCI115885 [doi]
PST - ppublish
SO  - J Clin Invest. 1992 Aug;90(2):488-96. doi: 10.1172/JCI115885.