Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030794 (pelvic pain)
 4,056 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RANTES (regulated on activation, normal T cell expressed and secreted) is synthesized by endometrial and endometriotic stromal cells and circulates in peritoneal fluid. Reports indicate that medroxyprogesterone acetate (MPA) is clinically effective in alleviating pelvic pain in the majority of endometriosis patients, which leads us to hypothesize that MPA may be antiinflammatory. Prolonged treatment (8 d) with MPA resulted in 36% and 50% decreases in luciferase activity and RANTES protein production, respectively, whereas shorter treatment (2 or 4 d) with MPA had no significant effect. We also observed that 8 d of MPA increased PR expression. Both effects were blocked by RU486. Cotransfection of endometrial stromal cells with PR enhanced the effects mediated by endogenous PR. In addition, its action via progesterone response element cis-elements, PR appeared to inhibit trans-activation of a nuclear factor-kappaB-responsive element, further suppressing RANTES expression. These studies indicate that prolonged progestin exposure down-regulates endometrial RANTES gene transcription in vitro. The effect is PR dependent and mediated in part through a nuclear factor-kappaB pathway. The clinical effectiveness of chronic progestin treatment in endometriosis-associated pelvic pain may be attributed to its inhibition of RANTES production and its suppression of inflammatory responses in the pelvis.
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PMID:Long-term progestin treatment inhibits RANTES (regulated on activation, normal T cell expressed and secreted) gene expression in human endometrial stromal cells. 1205 Feb 7

Chemoattraction of macrophages into the peritoneal cavity is one of the important characteristics in patients with endometriosis. An inflammatory response is postulated to be responsible for infertility and pelvic pain associated with this syndrome. The present in vivo studies were designed to test if thiazolidinediones (TZDs), activators of peroxisome proliferator activated receptor gamma, could inhibit monocyte chemotaxis in a murine model. TZDs were first used as orally bioavailable insulin-sensitizing agents. They are currently under investigation in the treatment of inflammatory diseases, including arthritis or colitis. Intraperitoneal injection of thioglycollate was used to elicit high numbers of activated peritoneal macrophages in female mice. Concomitant peritoneal injection of ciglitazone, a member of the TZD family, significantly reduced the number of macrophages. When cultured and stimulated by tumor necrosis factor alpha, these peritoneal macrophages also secreted less RANTES and less IL-1beta protein. This animal model suggests that treatment of endometriosis patients with TZDs may diminish symptoms associated with intraperitoneal inflammation.
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PMID:Thiazolidinedione inhibition of peritoneal inflammation. 1262 47