TY - JOUR
T1 - Suppression of human synovial cell proliferation by dihomo‐γ‐linolenic acid
AU - Baker, Daniel G.
AU - Krakauer, Kathrin A.
AU - Tate, Guillermo
AU - Laposata, Michael
AU - Zurier, Robert B.
PY - 1989/10
Y1 - 1989/10
N2 - Prostaglandin E1 (PGE1) and oils enriched in its precursor fatty acids suppress inflammation and joint tissue injury in several animal models. Since synovial cell proliferation is a hallmark of rheumatoid arthritis, we studied the effect of dihomo‐γ‐linolenic acid (DGLA), an immediate precursor of PGE1, on the growth of human adherent synovial cells (ASC) in tissue culture. When stimulated by appropriate concentrations of recombinant interleukin‐1β (rIL‐1β), ASC proliferate and produce PGE. DGLA‐enriched medium suppressed both baseline and rIL‐1β–stimulated ASC growth fivefold, compared with medium supplemented with arachidonic acid. Indomethacin reduced the effect of the DGLA. Synovial cells incorporated the DGLA, and rIL‐1β–stimulated cells that were incubated with DGLA exhibited a 14‐fold increase in PGE1 (to 25.2 ± 6.0 ng/ml, mean ± SD) and a 70% decrease in PGE2 (to 25.2 ± 4.2 ng/ml) compared with cells in control medium. At equivalent concentrations (5 × 10−7M), PGE1 increased the level of cellular cAMP to a greater extent than did PGE2 (16.8 ± 2.0 pmoles versus 4.3 ± 1.9 pmoles, mean ± SEM). Exogenous PGE1 was also a more effective inhibitor of cell growth. Similarly, cAMP concentrations in cells exposed to DGLA for 6 hours were greater than concentrations in arachidonic acidenriched cultures (17.8 ± 3.3 pmoles versus 2.1 ± 2.0 pmoles). These observations suggest that DGLA can restrain ASC growth, an effect which may be due to its capacity to increase PGE1 production and subsequent cellular cAMP concentration.
AB - Prostaglandin E1 (PGE1) and oils enriched in its precursor fatty acids suppress inflammation and joint tissue injury in several animal models. Since synovial cell proliferation is a hallmark of rheumatoid arthritis, we studied the effect of dihomo‐γ‐linolenic acid (DGLA), an immediate precursor of PGE1, on the growth of human adherent synovial cells (ASC) in tissue culture. When stimulated by appropriate concentrations of recombinant interleukin‐1β (rIL‐1β), ASC proliferate and produce PGE. DGLA‐enriched medium suppressed both baseline and rIL‐1β–stimulated ASC growth fivefold, compared with medium supplemented with arachidonic acid. Indomethacin reduced the effect of the DGLA. Synovial cells incorporated the DGLA, and rIL‐1β–stimulated cells that were incubated with DGLA exhibited a 14‐fold increase in PGE1 (to 25.2 ± 6.0 ng/ml, mean ± SD) and a 70% decrease in PGE2 (to 25.2 ± 4.2 ng/ml) compared with cells in control medium. At equivalent concentrations (5 × 10−7M), PGE1 increased the level of cellular cAMP to a greater extent than did PGE2 (16.8 ± 2.0 pmoles versus 4.3 ± 1.9 pmoles, mean ± SEM). Exogenous PGE1 was also a more effective inhibitor of cell growth. Similarly, cAMP concentrations in cells exposed to DGLA for 6 hours were greater than concentrations in arachidonic acidenriched cultures (17.8 ± 3.3 pmoles versus 2.1 ± 2.0 pmoles). These observations suggest that DGLA can restrain ASC growth, an effect which may be due to its capacity to increase PGE1 production and subsequent cellular cAMP concentration.
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U2 - 10.1002/anr.1780321013
DO - 10.1002/anr.1780321013
M3 - Article
C2 - 2553025
AN - SCOPUS:0024419760
VL - 32
SP - 1273
EP - 1281
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
SN - 2326-5191
IS - 10
ER -