title: Activation of μ opioid receptors modulates inflammation in acute experimental colitis.
abstract: BACKGROUND
  μ 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.
  
  
  METHODS
  C57BL/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.
  
  
  RESULTS
  DSS 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
  μOR 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.
authors.affiliation: CURE Digestive Diseases Research Center, Digestive Diseases Division, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA; Department of Medicine, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Anselmi
authors.forename: J
authors.initials: J
authors.lastname: Huynh
authors.forename: C
authors.initials: C
authors.lastname: Duraffourd
authors.forename: I
authors.initials: I
authors.lastname: Jaramillo
authors.forename: G
authors.initials: G
authors.lastname: Vegezzi
authors.forename: F
authors.initials: F
authors.lastname: Saccani
authors.forename: E
authors.initials: E
authors.lastname: Boschetti
authors.forename: N C
authors.initials: NC
authors.lastname: Brecha
authors.forename: R
authors.initials: R
authors.lastname: De Giorgio
authors.forename: C
authors.initials: C
authors.lastname: Sternini
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism*; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D016207:Cytokines; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016264:Dextran Sulfate
keywords: antiapoptotic factor; cytokines; inflammatory indexes; transcriptional nuclear factor-kB