Monocyte eukaryotic initiation factor 2 signaling differentiates 17-hydroxy-docosahexaenoic acid levels and pain

Summary: 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 st...

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Main Authors: Peter R.W. Gowler, Asta Arendt-Tranholm, James Turnbull, Rakesh R. Jha, David Onion, Tony Kelly, Afroditi Kouraki, Paul Millns, Sameer Gohir, Susan Franks, David A. Barrett, Ana M. Valdes, Victoria Chapman
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225001221
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Summary:Summary: 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.
ISSN:2589-0042