1. Activation of μ opioid receptors modulates inflammation in acute experimental colitis
- Author
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Anselmi, L, Huynh, J, Duraffourd, C, Jaramillo, I, Vegezzi, G, Saccani, F, Boschetti, E, Brecha, NC, De Giorgio, R, and Sternini, C
- Subjects
Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Digestive Diseases ,Genetics ,Animals ,Colitis ,Cytokines ,Dextran Sulfate ,Disease Models ,Animal ,Enkephalin ,Ala(2)-MePhe(4)-Gly(5)- ,Inflammation ,Mice ,Mice ,Inbred C57BL ,Receptors ,Opioid ,mu ,antiapoptotic factor ,cytokines ,inflammatory indexes ,transcriptional nuclear factor-kB ,Antiapoptotic factor ,Inflammatory indexes ,Transcriptional nuclear factor-kB ,Clinical Sciences ,Neurosciences ,Medical Physiology ,Gastroenterology & Hepatology ,Clinical sciences ,Medical physiology - Abstract
Backgroundμ opioid receptors (μORs) are expressed by neurons and inflammatory cells, and mediate immune response. We tested whether activation of peripheral μORs ameliorates the acute and delayed phase of colitis.MethodsC57BL/6J mice were treated with 3% dextran sodium sulfate (DSS) in water, 5 days with or without the peripherally acting μOR agonist, [D-Ala2, N-Me-Phe4, Gly5-ol]-Enkephalin (DAMGO) or with DAMGO+μOR antagonist at day 2-5, then euthanized. Other mice received DSS followed by water for 4 weeks, or DSS with DAMGO starting at day 2 of DSS for 2 or 3 weeks followed by water, then euthanized at 4 weeks. Disease activity index (DAI), histological damage, and myeloperoxidase assay (MPO), as index of neutrophil infiltration, were evaluated. Cytokines and μOR mRNAs were measured with RT-PCR, and nuclear factor-kB (NF-kB), the antiapoptotic factor Bcl-xL, and caspase 3 and 7 with Western blot.Key resultsDSS induced acute colitis with elevated DAI, tissue damage, apoptosis and increased MPO, cytokines, μOR mRNA, and NF-kB. DAMGO significantly reduced DAI, inflammatory indexes, cytokines, caspases, and NF-kB, and upregulated Bcl-xL, effects prevented by μOR antagonist. In DSS mice plus 4 weeks of water, DAI, NF-kB, and μOR were normal, whereas MPO, histological damage, and cytokines were still elevated; DAMGO did not reduce inflammation, and did not upregulate Bcl-xL.Conclusions & inferencesμOR activation ameliorated the acute but not the delayed phase of DSS colitis by reducing cytokines, likely through activation of the antiapoptotic factor, Bcl-xL, and suppression of NF-kB, a potentiator of inflammation.
- Published
- 2015