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  2. Prostaglandin E3 attenuates macrophage-associated inflammation and prostate tumour growth by modulating polarization

Prostaglandin E3 attenuates macrophage-associated inflammation and prostate tumour growth by modulating polarization

  • J Cell Mol Med. 2021 Jun;25(12):5586-5601. doi: 10.1111/jcmm.16570.
Jing Cui 1 2 Kai Shan 1 2 Qin Yang 1 2 Yumin Qi 1 2 Hongyan Qu 1 2 Jiaqi Li 1 2 Rong Wang 1 2 Lingling Jia 1 2 Wei Chen 2 Ninghan Feng 3 Yong Q Chen 1 2
Affiliations

Affiliations

  • 1 Wuxi School of Medicine, Jiangnan University, Wuxi, China.
  • 2 School of Food Science and Technology, Jiangnan University, Wuxi, China.
  • 3 Department of Urology, Wuxi No. 2 People's Hospital, Wuxi, China.
Abstract

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 E3 (PGE3 ) is an eicosanoid derived from eicosapentaenoic acid, which is converted by cyclooxygenase, followed by prostaglandin E synthase successively. We found that PGE3 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 PGE3 had no direct effect on the growth of prostate Cancer cells in vitro, PGE3 could inhibit prostate Cancer in vivo in a nude mouse model of neoplasia. Notably, we found that PGE3 significantly inhibited prostate Cancer cell growth in a Cancer cell-macrophage co-culture system. Experimental results showed that PGE3 inhibited the polarization of tumour-associated M2 macrophages (TAM), consequently producing indirect anti-tumour activity. Mechanistically, we identified that PGE3 regulated the expression and activation of protein kinase A, which is critical for macrophage polarization. In summary, this study indicates that PGE3 can selectively promote M2a polarization, while inhibiting M1 and TAM polarization, thus exerting an anti-inflammatory effect and anti-tumour effect in prostate Cancer.

Keywords

macrophage polarization; prostaglandin E3; protein kinase A; tumour-associated macrophage.

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