PMID- 9528904
OWN - NLM
STAT- MEDLINE
DCOM- 19980413
LR  - 20191211
IS  - 0009-9104 (Print)
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Linking)
VI  - 111
IP  - 3
DP  - 1998 Mar
TI  - Tenidap decreases IL-8 and monocyte chemotactic peptide-1 (MCP-1) mRNA expression 
      in the synovial tissue of rabbits with antigen arthritis and in cultured synovial 
      cells.
PG  - 588-96
AB  - Since IL-8 and MCP-1 are chemoattractant proteins that participate in the 
      recruitment of inflammatory cells into the arthritic joint, we examined the 
      effects of tenidap, a new anti-inflammatory drug of the oxindole family, on IL-8 
      and MCP-1 expression in the joints of rabbits with acute antigen arthritis. The 
      model was induced by injecting 5 mg/ml ovalbumin into the knees of 20 
      preimmunized rabbits. Animals were randomized into two groups: treated with 
      tenidap (15 mg/kg per 12 h), or untreated. The effect of tenidap treatment was 
      evaluated on chemokine production in synovial membranes of rabbits with arthritis 
      and in cultured monocytic and synovial cells (SC). By immunoperoxidase staining, 
      chemokines were localized in the synovial tissue. Chemokine messenger RNA levels 
      in the synovial membranes and in cultured cells were analysed by reverse 
      transcription-polymerase chain reaction (RT-PCR). At the end of the study, 
      tenidap significantly reduced neutrophil infiltration into the joint cavity 
      (27+/-4 x 10(6) cells/ml versus 45+/-6 x 10(6) cells/ml in untreated; P<0.05), 
      and synovial effusion (134+/-15 microl versus 236+/-19 microl in untreated; 
      P<0.005). Untreated rabbits showed synovial membrane up-regulation in mRNA 
      expression of IL-8 and MCP-1 (11- and seven-fold versus healthy rabbits, 
      respectively) that was markedly decreased by tenidap (two- and three-fold versus 
      healthy rabbits, respectively). IL-8 and MCP-1 were localized in the synovial 
      tissue in a perivascular pattern and areas of the interstitium and lining, mostly 
      coinciding with cell infiltration. Tenidap also reduced the accumulation of IL-8 
      and MCP-1 proteins. In cultured synovial and monocytic cells, tumour necrosis 
      factor-alpha (TNF-alpha) elicited an increase in gene expression of IL-8 (four- 
      and nine-fold, respectively) and MCP-1 (nine- and four-fold, respectively) that 
      was significantly reversed in both cell types by 10 microM tenidap. These results 
      suggest that the beneficial effect of tenidap in acute antigen arthritis could be 
      related to the down-regulation in gene expression and synthesis of IL-8 and 
      MCP-1, two key chemokines involved in the recruitment of inflammatory cells.
FAU - Palacios, I
AU  - Palacios I
AD  - Rheumatology Division, Fundacion Jimenez Diaz, Universidad Autonoma, Madrid, 
      Spain.
FAU - Lopez-Armada, M J
AU  - Lopez-Armada MJ
FAU - Hernandez, P
AU  - Hernandez P
FAU - Sanchez-Pernaute, O
AU  - Sanchez-Pernaute O
FAU - Gutierrez, S
AU  - Gutierrez S
FAU - Miguelez, R
AU  - Miguelez R
FAU - Martinez, J
AU  - Martinez J
FAU - Egido, J
AU  - Egido J
FAU - Herrero-Beaumont, G
AU  - Herrero-Beaumont G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Antigens)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokines)
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Indoles)
RN  - 0 (Interleukin-8)
RN  - 0 (Oxindoles)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9K7CJ74ONH (tenidap)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Antigens
MH  - Arthritis, Experimental/genetics/*metabolism
MH  - Cells, Cultured
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - Chemokines/biosynthesis/genetics
MH  - Cyclooxygenase Inhibitors/*pharmacology
MH  - Disease Models, Animal
MH  - Down-Regulation
MH  - Gene Expression
MH  - Indoles/*pharmacology
MH  - Interleukin-8/*biosynthesis/genetics
MH  - Leukocytes/metabolism
MH  - Oxindoles
MH  - RNA, Messenger/genetics/*metabolism
MH  - Rabbits
MH  - Synovial Membrane/*drug effects/*metabolism
MH  - Tumor Necrosis Factor-alpha/biosynthesis
PMC - PMC1904886
EDAT- 1998/04/07 00:00
MHDA- 1998/04/07 00:01
PMCR- 1999/03/01
CRDT- 1998/04/07 00:00
PHST- 1998/04/07 00:00 [pubmed]
PHST- 1998/04/07 00:01 [medline]
PHST- 1998/04/07 00:00 [entrez]
PHST- 1999/03/01 00:00 [pmc-release]
AID - 10.1046/j.1365-2249.1998.00530.x [doi]
PST - ppublish
SO  - Clin Exp Immunol. 1998 Mar;111(3):588-96. doi: 10.1046/j.1365-2249.1998.00530.x.