Rifampin inhibits prostaglandin E2 production and arachidonic acid release in human alveolar epithelial cells.
Rifampin, a potent antimicrobial agent, is a major drug in the treatment of tuberculosis. There is evidence that rifampin also serves as an immunomodulator. Based on findings that arachidonic acid and its metabolites are involved in the pathogeneses of Mycobacterium tuberculosis infections, we investigated whether rifampin affects prostaglandin E(2) (PGE(2)) production in human alveolar epithelial cells stimulated with interleukin-1beta. Rifampin caused a dose-dependent inhibition of PGE(2) production. At doses of 100, 50, and 25 microg/ml, it inhibited PGE(2) production by 75%, 59%, and 45%, respectively (P < 0.001). Regarding the mechanism involved, rifampin caused a time- and dose-dependent inhibition of arachidonic acid release from the alveolar cells. At doses of 100, 50, 25, and 10 mug/ml, it significantly inhibited the release of arachidonic acid by 93%, 64%, 58%, and 35%, respectively (P < 0.001). Rifampin did not affect the phosphorylation of cytosolic phospholipase A(2) or the expression of cyclooxygenase-2. The inhibition of PGE(2), and presumably other arachidonic acid products, probably contributes to the efficacy of rifampin in the treatment of tuberculosis and may explain some of its adverse effects.
Yuhas
Yael
Y
Laboratory of Infectious Diseases, Felsenstein Medical Research Center, Beilinson Campus, Petach Tikva 49100, Israel. yuhas@post.tau.ac.il
Azoulay-Alfaguter
Inbar
I
Berent
Eva
E
Ashkenazi
Shai
S
D016718:Arachidonic Acid / Q000096:biosynthesis / Q000378:metabolism*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis*; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D054467:Phospholipases A2 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism; D012293:Rifampin / Q000494:pharmacology*
D053583:Interleukin-1beta; D016718:Arachidonic Acid; D051546:Cyclooxygenase 2; D054467:Phospholipases A2; D015232:Dinoprostone; D012293:Rifampin