High Expression of IL-1RI and EP₂ Receptors in the IL-1β/COX-2 Pathway, and a New Alternative to Non-Steroidal Drugs-Osthole in Inhibition COX-2.

BACKGROUND: Osthole (7-methoxy-8-isopentenylcoumarin) is natural coumarin isolated from the fruit of Cnidium monnieri (L.) Cusson , which is commonly used in medical practice of traditional Chinese medicine (TCM) in various diseases including allergies and asthma disorders.

PURPOSE: Osthole was tested for the anti-histamine, anti-allergic, and inhibitory effects of COX-2 (cyclooxygenase-2) in children with diagnosed allergies. Additionally, we hypothesize that stated alterations in children with diagnosed allergies including increased expression of interleukin 1-β receptor type 1 ( IL-1 type I ) and E-prostanoid ( EP ) 2 receptors, as well as raised expression, production, and activity of COX-2 and IL-1β in incubated medium are approximately connected. Furthermore, we establish the mechanisms included in the changed regulation of the COX-2 pathway and determine whether osthole may be COX-2 inhibitor in peripheral blood mononuclear cells (PBMCs).

METHOD: PBMCs were obtained from peripheral blood of healthy children (control, n = 28) and patients with diagnosed allergies (allergy, n = 30). Expression of the autocrine loop components regulating PGE₂ production and signaling namely IL-1 type I receptor ( IL-1RI ), cyclooksygenaze-2 ( COX-2 ), E-prostanoid ( EP ) 2 , and also histamine receptor-1 ( HRH-1 ) was assessed at baseline and after stimulation with histamine, osthole, and a mixture of histamine/osthole 1:2 ( v/v ). This comprised the expression of histamine receptor 1 ( HRH-1), IL-1RI, COX-2, EP ₂ receptor, and the secretion of IL-1β and COX-2 in cultured media and sera.

RESULTS: Compared with control group, basal mRNA expression levels of HRH-1, IL-1RI, COX-2 , and EP ₂ were higher in the allergy group. Histamine-induced EP ₂ and COX-2 expression mRNA levels were also increased.

CONCLUSIONS: Osthole successively inhibits PGE ₂ and COX-2 mRNA expression. Furthermore, osthole reduces the secretion of COX-2 protein in signaling cellular mechanisms. Changed EP ₂ expression in children with allergies provides higher IL-1RI induction, increasing IL-1β capacity to increase COX-2 expression. This effects in higher PGE₂ production, which in turn increases its capability to induce IL-1RI.