title: Characterization of porcine NLRP3 inflammasome activation and its upstream mechanism.
abstract: Inflammasomes, which are intracellular sensors of endogenous or exogenous danger signals, activate caspase-1, resulting in interleukin (IL)-1β maturation. Although most studies on inflammasomes have been performed in human and/or mouse-derived macrophages, porcine inflammasome activation has not been elucidated even though pigs are considered one of the best animal models for translational and preclinical investigations. In this study, we optimized detection of porcine IL-1β secretion, which is the most well established indicator of inflammasome activation, and compared inflammasome activation between miniature and domestic pigs as well as between porcine and murine macrophages. In our results, anti-sera against murine IL-1β had higher affinity to porcine IL-1β than anti-sera against human IL-1β, even though the amino acid sequence of porcine IL-1β was more similar to that of human IL-1β. In addition, there was no significant difference in inflammasome activation between miniature and domestic pigs. Furthermore, well established inflammasome triggers (ATP, nigericin, and crystals) in humans and mice had similar effects on porcine NLRP3 inflammasome activation. We further elucidated the upstream signaling pathway of porcine inflammasome activation using pharmacological inhibitors. Similar to the mechanisms of inflammasome activation in humans and mice, potassium efflux and reactive oxygen species generation were confirmed as key pathways in porcine inflammasome activation. Thus, inflammasome activation in pigs is not different from that in humans or mice.
authors.affiliation: College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chucheon, 200-701, Republic of Korea.
authors.forename: Jeeyoung
authors.initials: J
authors.lastname: Kim
authors.forename: Huijeong
authors.initials: H
authors.lastname: Ahn
authors.forename: Heung-Myong
authors.initials: HM
authors.lastname: Woo
authors.forename: Eunsong
authors.initials: E
authors.lastname: Lee
authors.forename: Geun-Shik
authors.initials: GS
authors.lastname: Lee
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D058847:Inflammasomes / Q000187:drug effects / Q000502:physiology*; D053583:Interleukin-1beta / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008264:Macrophages / Q000502:physiology; D051379:Mice; D009550:Nigericin / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction; D013552:Swine
chemical_list: D058847:Inflammasomes; D053583:Interleukin-1beta; D007476:Ionophores; D017382:Reactive Oxygen Species; D018160:Receptors, Cytoplasmic and Nuclear; D000255:Adenosine Triphosphate; D009550:Nigericin; D011188:Potassium