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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Elsevier
2025-02-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225001221 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Peter R.W. Gowler |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d8b39fbbcd8448cbbef12116e8512af1 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-d8b39fbbcd8448cbbef12116e8512af12025-02-08T05:00:51ZengElsevieriScience2589-00422025-02-01282111862Monocyte eukaryotic initiation factor 2 signaling differentiates 17-hydroxy-docosahexaenoic acid levels and painPeter R.W. Gowler0Asta Arendt-Tranholm1James Turnbull2Rakesh R. Jha3David Onion4Tony Kelly5Afroditi Kouraki6Paul Millns7Sameer Gohir8Susan Franks9David A. Barrett10Ana M. Valdes11Victoria Chapman12Pain Centre Versus Arthritis and NIHR Nottingham Biomedical Research Centre, School of Life Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UKPain Centre Versus Arthritis and NIHR Nottingham Biomedical Research Centre, School of Life Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UKPain Centre Versus Arthritis and NIHR Nottingham Biomedical Research Centre, School of Life Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK; Centre for Analytical Bioscience, Advanced Materials and Healthcare Technologies Division and NIHR Nottingham Biomedical Research Centre, School of Pharmacy, University of Nottingham, Nottingham, UKPain Centre Versus Arthritis and NIHR Nottingham Biomedical Research Centre, School of Life Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK; Centre for Analytical Bioscience, Advanced Materials and Healthcare Technologies Division and NIHR Nottingham Biomedical Research Centre, School of Pharmacy, University of Nottingham, Nottingham, UKFlow Cytometry Facility, School of Life Sciences, University of Nottingham, Nottingham, UKPain Centre Versus Arthritis and NIHR Nottingham Biomedical Research Centre, School of Medicine, University of Nottingham, Nottingham, UKPain Centre Versus Arthritis and NIHR Nottingham Biomedical Research Centre, School of Medicine, University of Nottingham, Nottingham, UKPain Centre Versus Arthritis and NIHR Nottingham Biomedical Research Centre, School of Life Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UKPain Centre Versus Arthritis and NIHR Nottingham Biomedical Research Centre, School of Medicine, University of Nottingham, Nottingham, UKSchool of Mathematical Sciences, University of Nottingham, Nottingham, UKCentre for Analytical Bioscience, Advanced Materials and Healthcare Technologies Division and NIHR Nottingham Biomedical Research Centre, School of Pharmacy, University of Nottingham, Nottingham, UKPain Centre Versus Arthritis and NIHR Nottingham Biomedical Research Centre, School of Medicine, University of Nottingham, Nottingham, UKPain Centre Versus Arthritis and NIHR Nottingham Biomedical Research Centre, School of Life Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004225001221Biological sciencesMolecular neuroscienceNeuroscience |
| spellingShingle | 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 Monocyte eukaryotic initiation factor 2 signaling differentiates 17-hydroxy-docosahexaenoic acid levels and pain iScience Biological sciences Molecular neuroscience Neuroscience |
| title | Monocyte eukaryotic initiation factor 2 signaling differentiates 17-hydroxy-docosahexaenoic acid levels and pain |
| title_full | Monocyte eukaryotic initiation factor 2 signaling differentiates 17-hydroxy-docosahexaenoic acid levels and pain |
| title_fullStr | Monocyte eukaryotic initiation factor 2 signaling differentiates 17-hydroxy-docosahexaenoic acid levels and pain |
| title_full_unstemmed | Monocyte eukaryotic initiation factor 2 signaling differentiates 17-hydroxy-docosahexaenoic acid levels and pain |
| title_short | Monocyte eukaryotic initiation factor 2 signaling differentiates 17-hydroxy-docosahexaenoic acid levels and pain |
| title_sort | monocyte eukaryotic initiation factor 2 signaling differentiates 17 hydroxy docosahexaenoic acid levels and pain |
| topic | Biological sciences Molecular neuroscience Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225001221 |
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