title: Antecedent hydrogen sulfide elicits an anti-inflammatory phenotype in postischemic murine small intestine: role of heme oxygenase-1.
abstract: We recently demonstrated that preconditioning with an exogenous hydrogen sulfide donor (NaHS-PC) 24 h before ischemia and reperfusion (I/R) causes postcapillary venules to shift to an anti-inflammatory phenotype in C57BL/6J wild-type (WT) mice such that these vessels fail to support increases in postischemic leukocyte rolling (LR) and leukocyte adhesion (LA). The objective of the present study was to determine whether heme oxygenase-1 (HO-1) is a mediator of these anti-inflammatory effects noted during I/R in mice preconditioned with NaHS. Intravital fluorescence microscopy was used to visualize LR and LA in single postcapillary venules of the murine small intestine. I/R induced marked increases in LR and LA, effects that were prevented by NaHS-PC. Treatment with the HO inhibitor tin protoporphyrin IX, but not the inactive protoporphyrin CuPPIX, just before reperfusion prevented the anti-inflammatory effects of antecedent NaHS. The anti-inflammatory effects of NaHS-PC were mimicked by preconditioning with hemin, an agent that induces HO-1 expression. We then evaluated the effect of NaHS as a preconditioning stimulus in mice that were genetically deficient in HO-1 (HO-1(-/-) on an H129 background with appropriate WT strain controls). NaHS-PC was ineffective in HO-1(-/-) mice. Our work indicates that HO-1 serves as an effector of the anti-inflammatory effects of NaHS-PC during I/R 24 h later.
authors.affiliation: Department of Medical Pharmacology and Physiology, University of Missouri-Columbia School of Medicine, Columbia, Missouri 65212, USA.
authors.forename: Mozow Y
authors.initials: MY
authors.lastname: Zuidema
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Peyton
authors.forename: William P
authors.initials: WP
authors.lastname: Fay
authors.forename: William
authors.initials: W
authors.lastname: Durante
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Korthuis
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007421:Intestine, Small / Q000098:blood supply*; D036904:Leukocyte Rolling / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D010641:Phenotype; D011524:Protoporphyrins / Q000494:pharmacology; D015427:Reperfusion Injury / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D013440:Sulfides / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors; D014699:Venules / Q000187:drug effects / Q000201:enzymology / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D008665:Metalloporphyrins; D011524:Protoporphyrins; D013440:Sulfides; C032628:tin protoporphyrin IX; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; C025451:sodium bisulfide; D006862:Hydrogen Sulfide