Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients |
| |
| Institution: | 1. Nerve-Gut Research Laboratory, Discipline of Medicine, Faculty of Health Sciences, The University of Adelaide, Adelaide, SA 5000, Australia;2. Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, SA 5000, Australia;3. Leukocyte Biology Laboratory, Women’s and Children’s Health Research Institute, North Adelaide, SA 5006, Australia;4. Department of Gastroenterology, Flinders Medical Centre, Flinders University, Bedford Park, SA 5042, Australia;5. Adelaide Proteomics Centre, School of Molecular Biomedical Science, The University of Adelaide, Adelaide, SA 5005, Australia;6. Discipline of Paediatrics, Faculty of Health Sciences, University of Adelaide, SA 5005, Australia;7. SA Pathology, Adelaide, SA 5000, Australia;1. Institut National de la Santé et de la Recherche Médicale, Unité 1138, Paris F-75006, France;2. Université de Technologie de Compiègne, Compiègne F-60205, France;3. Centre de Recherche des Cordeliers, Equipe – Immunopathology and Therapeutic Immunointervention, Paris F-75006, France;4. Sorbonne Universités, UPMC Univ Paris 06, UMR S 1138, Paris F-75006, France;5. Armand Trousseau Children Hospital, Biochemistry Department, “Allergy & Environment” Group, Paris F-75012, France;6. Université Paris Descartes, Sorbonne Paris Cité, UMR S 1138, Paris F-75006, France;7. International Associated Laboratory IMPACT (Institut National de la Santé et de la Recherche Médicale, France – Indian Council of Medical Research, India), National Institute of Immunohaematology, Mumbai 400012, India;1. Department of Pharmacology, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), School of Pharmacy, Instituto de Investigación Biosanitaria ibs.GRANADA, University of Granada, Granada, Spain;2. Department of Biochemistry and Molecular Biology II, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), School of Pharmacy, Instituto de Investigación Biosanitaria ibs.GRANADA, University of Granada, Granada, Spain |
| |
| Abstract: | Alterations in the neuro-immune axis contribute toward viscerosensory nerve sensitivity and symptoms in Irritable Bowel Syndrome (IBS). Inhibitory factors secreted from immune cells inhibit colo-rectal afferents in health, and loss of this inhibition may lead to hypersensitivity and symptoms. We aimed to determine the immune cell type(s) responsible for opioid secretion in humans and whether this is altered in patients with IBS. The β-endorphin content of specific immune cell lineages in peripheral blood and colonic mucosal biopsies were compared between healthy subjects (HS) and IBS patients. Peripheral blood mononuclear cell (PBMC) supernatants from HS and IBS patients were applied to colo-rectal sensory afferent endings in mice with post-inflammatory chronic visceral hypersensitivity (CVH). β-Endorphin was identified predominantly in monocyte/macrophages relative to T or B cells in human PBMC and colonic lamina propria. Monocyte derived β-endorphin levels and colonic macrophage numbers were lower in IBS patients than healthy subjects. PBMC supernatants from healthy subjects had greater inhibitory effects on colo-rectal afferent mechanosensitivity than those from IBS patients. The inhibitory effects of PBMC supernatants were more prominent in CVH mice compared to healthy mice due to an increase in μ-opioid receptor expression in dorsal root ganglia neurons in CVH mice. Monocyte/macrophages are the predominant immune cell type responsible for β-endorphin secretion in humans. IBS patients have lower monocyte derived β-endorphin levels than healthy subjects, causing less inhibition of colonic afferent endings. Consequently, altered immune function contributes toward visceral hypersensitivity in IBS. |
| |
| Keywords: | Irritable Bowel Syndrome Visceral pain Opioid Neuro-immune Monocyte Macrophage |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
