Eicosanoid Signaling in Inflammatory Responses

Eicosanoids are bioactive lipid mediators derived predominantly from arachidonic acid that play pivotal roles in the modulation of inflammation and immune responses. Upon cellular activation by injury or infection, phospholipase A₂ liberates arachidonic acid from membrane phospholipids. This substrate is then converted via cyclooxygenase or lipoxygenase pathways into prostaglandins, thromboxanes, leukotrienes and oxoeicosanoids. These metabolites act locally through specific G-protein-coupled receptors to regulate vascular permeability, leukocyte chemotaxis, cytokine synthesis and resolution of inflammation. Dysregulation of eicosanoid signalling contributes to chronic inflammatory diseases, including arthritis, asthma and cancer, highlighting the therapeutic potential of targeting individual pathways or receptor subtypes. The intricate balance between pro-inflammatory and pro-resolving eicosanoids orchestrates both the initiation and termination of inflammatory cascades, with emerging evidence emphasising cross-talk between lipid mediators and steroid pathways to fine-tune cellular responses.

Research from Nature Portfolio

A seminal investigation has revealed that the oxoeicosanoid receptor OXER1, long recognised for mediating chemotactic signals in inflammatory cells, also serves as a membrane receptor for androgens in prostate cancer. In this study, testosterone was shown to bind directly to the OXER1 ligand-binding pocket, antagonising the actions of the endogenous ligand 5-oxo-ETE on downstream kinase cascades and cytoskeletal dynamics. This antagonism modulates cell migration and suggests a novel intersection between lipid and steroid signalling in tumour microenvironments, with implications for therapeutic strategies that target GPCRs to curb metastatic dissemination.

Eicosanoid Signaling in Inflammatory Responses publication trend

The graph below shows the total number of articles in eicosanoid signaling in inflammatory responses across all publications each year (not limited to Nature Index journals).

Technical terms

Eicosanoids: Endogenous lipid mediators derived from polyunsaturated fatty acids, notably arachidonic acid, that regulate inflammation and immunity.

Arachidonic acid: A 20-carbon polyunsaturated fatty acid released from membrane phospholipids and metabolised to various eicosanoids.

Phospholipase A₂: Enzyme that hydrolyses membrane phospholipids to release arachidonic acid.

G-protein-coupled receptor (GPCR): Cell-surface receptor family that transduces extracellular signals via heterotrimeric G proteins.

OXER1: A GPCR selective for oxoeicosanoids such as 5-oxo-ETE, implicated in leukocyte chemotaxis and steroid–lipid signalling cross-talk.

Chemoattractant: Substance that directs the migration of immune cells along a concentration gradient towards sites of inflammation or tissue damage.

References

1. Antagonizing effects of membrane-acting androgens on the eicosanoid receptor OXER1 in prostate cancer. Scientific Reports (2017).
2. 5-Oxo-ETE/OXER1: A Link between Tumor Cells and Macrophages Leading to Regulation of Migration. Molecules (2023).
3. Emerging Role of Phospholipase-Derived Cleavage Products in Regulating Eosinophil Activity: Focus on Lysophospholipids, Polyunsaturated Fatty Acids and Eicosanoids. International Journal of Molecular Sciences (2021).