| Abstrakt: |
Background μ opioid receptors ( μ ORs) are expressed by neurons and inflammatory cells, and mediate immune response. We tested whether activation of peripheral μ ORs ameliorates the acute and delayed phase of colitis. Methods C57 BL/6J mice were treated with 3% dextran sodium sulfate ( DSS) in water, 5 days with or without the peripherally acting μ OR agonist, [D-Ala2, N-Me-Phe4, Gly5-ol]-Enkephalin ( DAMGO) or with DAMGO+ μ OR 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 μ OR 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 Results DSS induced acute colitis with elevated DAI, tissue damage, apoptosis and increased MPO, cytokines, μ OR mRNA, and NF- kB. DAMGO significantly reduced DAI, inflammatory indexes, cytokines, caspases, and NF- kB, and upregulated Bcl- xL, effects prevented by μ OR antagonist. In DSS mice plus 4 weeks of water, DAI, NF- kB, and μ OR were normal, whereas MPO, histological damage, and cytokines were still elevated; DAMGO did not reduce inflammation, and did not upregulate Bcl- xL. Conclusions & Inferences μ OR 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. [ABSTRACT FROM AUTHOR] |
