Stimulation of prostaglandin e production by bacterial endotoxins in cultured human synovial fibroblasts

Abstract

E coli, shigella, salmonella, and cholera endotoxins stimulated prostaglandin E (PGE) production by cultured human synovial and foreskin fibroblasts. The minimal effective dose of Shigella endotoxin was 2 pg/ ml and a maximal response was observed at 10 pg/ml. PGE stimulation was first detected 7 hours after addition of cholera endotoxin. Stimulation by shigella endotoxin of both PGE and hyaluronic acid production was inhibited by indomethacin and aspirin. The present results suggest that PGE is a mediator of joint inflammation induced by endotoxins.A possible relationship between an infectious agent and joint inflammation has been repeatedly reported (1,2). It is possible that such an agent triggers an inflammatory process which in some cases is subsequently perpetuated by other factors (3). An intriguing observation, which has received no clear explanation, is the relationship between acute and chronic bowel diseases and arthritis (4). It is possible that endotoxins liberated from Gram negative bacteria in the bowel trigger an inflammatory reaction in the synovial membrane.There is ample evidence to suggest that prostaglandins are mediators of the inflammatory process (5,6). Others have reported stimulation of hyaluronic acid induced by bacterial endotoxins in human synovial fibroblast cultures (7). We have recently reported an interrelationship between stimulation of hyaluronic acid (HA) and that of prostaglandin E (PGE) in human cultured synovial fibroblasts (8). A preliminary study showed stimulation of both PGE and hyaluronic acid in human synovial fibroblast cultures by shigella endoThe present study reports the stimulation of prostaglandin E induced by different bacterial endotoxins in synovial and foreskin fibroblast cultures. MATERIALS AND METHODS toxin (9).Fibroblasts derived from synovial membranes obtained during meniscus tear operations of otherwise healthy persons were grown in monolayer cultures by methods previously reported by Castor et a1 (10). Human foreskin fibroblasts were obtained from Dr. Dalia Gurari-Rotman and Professor Michel Revel at the Weizmann Institute of Science, Israel. T-30 tissue culture flasks (5 ml of medium per flask) with siliconized rubber stoppers were inoculated with 0.5 X lo6 fibroblasts and incubated at 37OC. Synovial fibroblasts and HeLa cells were grown in medium CMRL 1066 (Gibco) (~W O ) , heat inactivated human serum (lo%), and fetal calf serum (lo%), supplemented with L-glutamine, penicillin, and streptomycin. Eagle's MEM (90%) with fetal calf serum (10%) was used for the foreskin monolayer cultures. "Purified" endotoxins (lipopolysaccharides) were purchased from Sigma

Absence of lipopolysaccharide in the Lyme disease spirochete, Borrelia burgdorferi

“…It did not stimulate prostaglandin E2 (PGE2) by monolayer cultures of rabbit synoviocytes. LPS from several gram-negative organisms stimulate PGE2 (20), and we have confirmed this finding in unpublished studies (R. J. Rothenberg and K. Takayama). Moreover, fraction E had a higher Rf value than the standard value for monophosphoryl lipid A.…”

Bacterial lipopolysaccharides induce in vitro degradation of cartilage matrix through chondrocyte activation.

“…Recently, Yaron et al. (17) Lipopolysaccharides Induce Cartilage Degradation . 2017 demonstrated that bacterial endotoxins could stimulate prostaglandin E production by synovial and foreskin fibroblasts.…”