Hemin and Cobalt Protoporphyrin Inhibit NLRP3 Inflammasome Activation by Enhancing Autophagy : A Novel Mechanism of Inflammasome Regulation

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Nurmi , K , Kareinen , I , Virkanen , J , Rajamaki , K , Kouri , V-P , Vaali , K , Levonen , A-L , Fyhrquist , N , Matikainen , S , Kovanen , P T & Eklund , K K 2017 , ' Hemin and Cobalt Protoporphyrin Inhibit NLRP3 Inflammasome Activation by Enhancing Autophagy : A Novel Mechanism of Inflammasome Regulation ' , Journal of innate immunity , vol. 9 , no. 1 , pp. 65-82 . https://doi.org/10.1159/000448894

Title: Hemin and Cobalt Protoporphyrin Inhibit NLRP3 Inflammasome Activation by Enhancing Autophagy : A Novel Mechanism of Inflammasome Regulation
Author: Nurmi, Katariina; Kareinen, Ilona; Virkanen, Juhani; Rajamaki, Kristiina; Kouri, Vesa-Petteri; Vaali, Kirsi; Levonen, Anna-Liisa; Fyhrquist, Nanna; Matikainen, Sampsa; Kovanen, Petri T.; Eklund, Kari K.
Other contributor: University of Helsinki, Wihuri Res Inst
University of Helsinki, Department of Geosciences and Geography
University of Helsinki, Clinicum
University of Helsinki, Department of Bacteriology and Immunology
University of Helsinki, Finnish Institute of Occupational Health (TTL)
University of Helsinki, HUS Internal Medicine and Rehabilitation
University of Helsinki, Clinicum








Date: 2017
Language: eng
Number of pages: 18
Belongs to series: Journal of innate immunity
ISSN: 1662-811X
DOI: https://doi.org/10.1159/000448894
URI: http://hdl.handle.net/10138/312772
Abstract: Inflammasomes are intracellular protein platforms, which, upon activation, produce the highly proinflammatory cytokines interleukin (IL)-1 beta and IL-18. Heme, hemin and their degradation products possess significant immunomodulatory functions. Here, we studied whether hemin regulates inflammasome function in macrophages. Both hemin and its derivative, cobalt protoporphyrin (CoPP), significantly reduced IL-1 beta secretion by cultured human primary macrophages, the human monocytic leukemia cell line and also mouse bone marrow-derived and peritoneal macrophages. Intraperitoneal administration of CoPP to mice prior to urate crystal-induced peritonitis alleviated IL-1 beta secretion to the peritoneal cavity. In cultured macrophages, hemin and CoPP inhibited NLRP3 inflammasome assembly by reducing the amount of intracellular apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC). The reduction of ASC was associated with enhanced autophagosome formation and autophagic flux. Inhibition of autophagy prevented the CoPP-induced depletion of ASC, implying that the depletion was caused by increased autophagy. Our data indicate that hemin functions as an endogenous negative regulator of the NLRP3 inflammasome. The inhibition is mediated via enhanced autophagy that results in increased degradation of ASC. This regulatory mechanism may provide a novel approach for the treatment of inflammasome-related diseases. (C) 2016 S. Karger AG, Basel
Subject: Inflannmasome
Autophagy
Macrophage
Hemin
Cobalt protoporphyrin
Heme oxygenase-1
LUNG INJURY
CATHEPSIN-B
OXYGENASE-1
LIPOPOLYSACCHARIDE
IL-1-BETA
CRYSTALS
MICE
EXPRESSION
IMMUNITY
DISEASES
3111 Biomedicine
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