A paracrine effect of 15 (S)-hydroxyeicosatetraenoic acid revealed in prostaglandin production by human follicular dendritic cell-like cells

• Published in: Prostaglandins & other lipid mediators 2020-12, Vol.151, p.106487, Article 106487
• Main Authors: Kim, Jini, Choe, Jongseon
• Format: Article
• Language: English
• Subjects: 15(S)-HETE; Cells, Cultured; Cyclooxygenase 2 - metabolism; Dendritic Cells, Follicular - cytology; Dendritic Cells, Follicular - metabolism; Follicular dendritic cell; Humans; Hydroxyeicosatetraenoic Acids - metabolism; Hydroxyeicosatetraenoic Acids - pharmacology; Interleukin-1beta - metabolism; Interleukin-1beta - pharmacology; Paracrine Communication - drug effects; PPAR gamma - genetics; PPAR gamma - metabolism; Prostaglandin; Prostaglandins - biosynthesis; Prostaglandins - metabolism
• ISSN: 1098-8823
• DOI: 10.1016/j.prostaglandins.2020.106487

•Uptake of 15(S)-HETE by FDC-like cells in culture.•Enhanced prostaglandin production by the combined addition of 15(S)-HETE and IL-1β.•PPARγ as the molecular mediator of the augmenting effect of 15(S)-HETE. Lipid mediators play active roles in each stage of inflammation under physiological and pathologic conditions. We have investigated the cellular source and functions of several prostanoids in the immune inflammatory responses using follicular dendritic cell (FDC)-like cells. In this study, we report a novel finding on the role of 15(S)- hydroxyeicosatetraenoic acid (HETE). Our observation of 15(S)-HETE uptake by FDC-like cells prompted to hypothesize that 15(S)-HETE might have a regulatory role in the other branch of eicosanoid production. The effects of 15(S)-HETE on COX-2 expression and prostaglandin (PG) production were analyzed by immunoblotting and specific enzyme immunoassays. The addition of 15(S)-HETE resulted in elevated levels of COX-2 expression and PG production. The enhanced PG production was not due to growth stimulation of FDC-like cells since 15(S)-HETE did not modulate FDC-like cell proliferation by the culture period of PG measurement. Peroxisome proliferator-activated receptor gamma (PPARγ) seems to mediate the augmenting activity as the antagonist GW9662 dose- dependently prevented 15(S)-HETE from increasing PG production. In addition, PPARγ protein expression was readily detected in FDC-like cells. These effects of 15(S)-HETE were displayed in the combined addition with IL-1β. Based on these results, we suggest that 15(S)-HETE is an inflammatory costimulator of FDC acting in a paracrine fashion.