Monocyte eukaryotic initiation factor 2 (EIF2) signalling differentiates 17-hydroxy-docosahexaenoic acid levels and pain

Gowler, Peter R.W.; Arendt-Tranholm, Asta; Turnbull, James; Jha, Rakesh R.; Onion, David; Kelly, Tony; Kouraki, Afroditi; Millns, Paul; Gohir, Sameer; Franks, Susan; Barrett, David A.; Valdes, Ana M.; Chapman, Victoria

Abstract

Our goal was to probe the potential transcriptomic basis for the relationship between plasma levels of the specialized pro-resolving precursor, 17-hydroxy-docosahexaenoic acid (17-HDHA) and chronic pain. Participants with osteoarthritis (average age of 62.3, 60% were female, n = 30) were stratified by levels of 17-HDHA and self-reported pain scores. RNAs from CD14++/CD16-/CD66b-/HLA-DR+ (classical) monocytes were sequenced and differentially expressed mRNAs were identified with DESeq2. QIAGEN ingenuity pathway analysis identified the top ranked canonical biological pathway to be eukaryotic initiation factor 2 (EIF2) signaling (lower activation level in the low 17-HDHA-high pain group compared to the high 17-HDHA-low pain group (Z score −3)), followed by EIF4 and P70S6K signaling pathways and mTOR signaling. Our approach provides insight into the biological pathways contributing to the association between 17-HDHA and chronic osteoarthritis (OA) pain, identifying EIF2 signaling, with known roles in osteoclast differentiation, OA pathology, and pain, as a potential downstream target.

Citation

Gowler, P. R., Arendt-Tranholm, A., Turnbull, J., Jha, R. R., Onion, D., Kelly, T., Kouraki, A., Millns, P., Gohir, S., Franks, S., Barrett, D. A., Valdes, A. M., & Chapman, V. (2025). Monocyte eukaryotic initiation factor 2 (EIF2) signalling differentiates 17-hydroxy-docosahexaenoic acid levels and pain. iScience, 28(2), Article 111862. https://doi.org/10.1016/j.isci.2025.111862

• Journal Article Type: Article
• Acceptance Date: Jan 17, 2025
• Online Publication Date: Jan 21, 2025
• Publication Date: 2025-01
• Deposit Date: Mar 6, 2025
• Publicly Available Date: Mar 7, 2025
• Journal: iScience
• Electronic ISSN: 2589-0042
• Publisher: Cell Press
• Peer Reviewed: Peer Reviewed
• Volume: 28
• Issue: 2
• Article Number: 111862
• DOI: https://doi.org/10.1016/j.isci.2025.111862
• Public URL: https://nottingham-repository.worktribe.com/output/44538594
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S2589004225001221