Open AccessProstaglandin E 3 attenuates macrophage‐associated inflammation and prostate tumour growth by modulating polarization
Author(s) -
Cui Jing,
Shan Kai,
Yang Qin,
Qi Yumin,
Qu Hongyan,
Li Jiaqi,
Wang Rong,
Jia Lingling,
Chen Wei,
Feng Ninghan,
Chen Yong Q.
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16570
Subject(s) - macrophage polarization , immune system , cancer research , prostaglandin e , prostate cancer , chemistry , cell growth , prostaglandin , prostaglandin e2 , inflammation , prostate , endocrinology , medicine , in vitro , macrophage , immunology , biology , biochemistry , cancer
Alternative polarization of macrophages regulates multiple biological processes. While M1‐polarized macrophages generally mediate rapid immune responses, M2‐polarized macrophages induce chronic and mild immune responses. In either case, polyunsaturated fatty acid (PUFA)‐derived lipid mediators act as both products and regulators of macrophages. Prostaglandin E 3 (PGE 3 ) is an eicosanoid derived from eicosapentaenoic acid, which is converted by cyclooxygenase, followed by prostaglandin E synthase successively. We found that PGE 3 played an anti‐inflammatory role by inhibiting LPS and interferon‐γ‐induced M1 polarization and promoting interleukin‐4‐mediated M2 polarization (M2a). Further, we found that although PGE 3 had no direct effect on the growth of prostate cancer cells in vitro, PGE 3 could inhibit prostate cancer in vivo in a nude mouse model of neoplasia. Notably, we found that PGE 3 significantly inhibited prostate cancer cell growth in a cancer cell‐macrophage co‐culture system. Experimental results showed that PGE 3 inhibited the polarization of tumour‐associated M2 macrophages (TAM), consequently producing indirect anti‐tumour activity. Mechanistically, we identified that PGE 3 regulated the expression and activation of protein kinase A, which is critical for macrophage polarization. In summary, this study indicates that PGE 3 can selectively promote M2a polarization, while inhibiting M1 and TAM polarization, thus exerting an anti‐inflammatory effect and anti‐tumour effect in prostate cancer.