2. Academic Validation
  3. Prostaglandin E2 alleviates inflammatory response and lung injury through EP4/cAMP/IKK/NF-κB pathway

Prostaglandin E2 alleviates inflammatory response and lung injury through EP4/cAMP/IKK/NF-κB pathway

  • Biochim Biophys Acta Mol Basis Dis. 2025 Mar 14;1871(5):167801. doi: 10.1016/j.bbadis.2025.167801.
Yelin Tang 1,  Weiting Pan 2,  Wenting Ding 2,  Xingye Pan 3,  Junyi Zhu 2,  Huiwen Chen 2,  Xiaona Zhu 4,  Jingyi Chen 2,  Zijun Cheng 2,  Yali Zhang 5,  Bing Zhang 6
Affiliations

Affiliations

  • 1 Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325600, China; Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Guangdong Food and Drug Vocational College, Guangzhou, Guangdong 510520, China.
  • 2 Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
  • 3 The First Affiliated Medical College of Southern Medical University, Guangzhou, Guangdong 510515, China.
  • 4 Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325600, China.
  • 5 Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325600, China; Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. Electronic address: ya-li000@wmu.edu.cn.
  • 6 Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325600, China. Electronic address: zhangbing197102@163.com.
PMID: 40090625 DOI: 10.1016/j.bbadis.2025.167801
Abstract

Purpose: Prostaglandin E2 (PGE2), a pivotal lipid metabolite, plays a dual role in inflammation, manifesting both pro-inflammatory and anti-inflammatory effects, which are significantly influenced by the cellular microenvironment and receptor subtype. Although recent studies have highlighted the anti-inflammatory potential of PGE2, its role in Toll-like Receptor (TLR)-associated inflammation and the underlying mechanisms have not fully elucidated. Consequently, the primary aim of this study was to assess the anti-inflammatory efficacy of PGE2 in TLR-related inflammation and to elucidate the associated mechanisms.

Methods: In vitro, the anti-inflammatory effect of PGE2 on TLR-related inflammation were investigated by measuring pro-inflammatory cytokine protein and gene levels using ELISA and RT-qPCR, respectively. Western blot analysis was used to explore the corresponding anti-inflammatory signaling pathways. In vivo, the anti-inflammatory effects of PGE2 were further validated using ALI and sepsis models, employing the PGE2 analog 16,16-dimethyl prostaglandin E2 (dmPGE2).

Results: The findings revealed that PGE2 inhibited the LPS-induced inflammatory response and activation of the IKK/NF-κB signaling pathway via the EP4 receptor-mediated downstream cAMP/PKA pathway. Additionally, PGE2 analog, dmPGE2, effectively mitigated pathological injury and the inflammatory response in lung tissue of mice subjected to LPS-induced ALI and sepsis. Notably, dmPGE2 suppressed LPS-induced activation of the IKK/NF-κB signaling pathway in lung tissue.

Conclusion: This study demonstrated that PGE2 can inhibit the IKK/NF-κB signaling pathway through the EP4/cAMP/PKA pathway, thereby alleviating the LPS-induced inflammatory response and providing a protective effect against LPS-induced ALI and sepsis. Consequently, PGE2 holds promise as a candidate for drug development aimed at preventing ALI and sepsis.

Keywords

Acute lung injury; Lipopolysaccharide; NF-κB; Prostaglandin E2; Sepsis.

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