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

• Published in: International journal of molecular sciences Vol. 20; no. 1; p. 186
• Main Authors: Kordulewska, Natalia Karolina, Cieślińska, Anna, Fiedorowicz, Ewa, Jarmołowska, Beata, Kostyra, Elżbieta
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07-01-2019; MDPI
• Subjects: Allergies; anti-inflammation; Case-Control Studies; Child; Child, Preschool; Control theory; Coumarins - chemistry; Coumarins - pharmacology; cultures in vitro; Cyclooxygenase 2 - metabolism; Cyclooxygenase Inhibitors - pharmacology; Cyclooxygenase-2; Cytokines; expression; Feedback loops; Female; Gene expression; Gene Expression Regulation - drug effects; Histamine; Histamine - chemistry; Histamine - pharmacology; Humans; Hypersensitivity; Hypersensitivity - genetics; Hypersensitivity - pathology; IL-1β; Interleukin 1; Interleukin 1 receptors; Interleukin-1beta - metabolism; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Male; Metabolism; Metabolites; Models, Biological; PBMCs; Peripheral blood mononuclear cells; Positive feedback; Prostaglandin E2; Prostaglandin-E synthase; Real time; Receptors, Histamine H1 - genetics; Receptors, Histamine H1 - metabolism; Receptors, Interleukin-1 Type I - genetics; Receptors, Interleukin-1 Type I - metabolism; Receptors, Prostaglandin E, EP2 Subtype - genetics; Receptors, Prostaglandin E, EP2 Subtype - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal Transduction - drug effects; anti-inflammation; expression; histamine; PBMCs; cultures in vitro
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20010186

Osthole (7-methoxy-8-isopentenylcoumarin) is natural coumarin isolated from the fruit of
(L.)
, which is commonly used in medical practice of traditional Chinese medicine (TCM) in various diseases including allergies and asthma disorders.
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 (
) and
(
)
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).
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
(
),
(
),
(
)
, and also
(
) was assessed at baseline and after stimulation with histamine, osthole, and a mixture of histamine/osthole 1:2 (
). This comprised the expression of histamine receptor 1 (
₂ receptor, and the secretion of IL-1β and COX-2 in cultured media and sera.
Compared with control group, basal mRNA expression levels of
, and
₂ were higher in the allergy group. Histamine-induced
₂ and
expression mRNA levels were also increased.
Osthole successively inhibits
₂ and
mRNA expression. Furthermore, osthole reduces the secretion of COX-2 protein in signaling cellular mechanisms. Changed
₂ expression in children with allergies provides higher
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.