The NLRP3 Inflammasome Fires Up Heme-Induced Inflammation in Hemolytic Conditions

Authors

Suruchi Salgar
Beatriz E Bolívar
Jonathan M Flanagan
Shaniqua J Anum
Lisa Bouchier-Hayes

Language

English

Publication Date

2-1-2023

Journal

Translational Research

DOI

36041706

PMID

PMC10351365

PMCID

10.1016/j.trsl.2022.08.011

PubMedCentral® Posted Date

7-17-2023

PubMedCentral® Full Text Version

Author MSS

Abstract

Overactive inflammatory responses are central to the pathophysiology of many hemolytic conditions including sickle cell disease. Excessive hemolysis leads to elevated serum levels of heme due to saturation of heme scavenging mechanisms. Extracellular heme has been shown to activate the NLRP3 inflammasome, leading to activation of caspase-1 and release of pro-inflammatory cytokines IL-1β and IL-18. Heme also activates the non-canonical inflammasome pathway, which may contribute to NLRP3 inflammasome formation and leads to pyroptosis, a type of inflammatory cell death. Some clinical studies indicate there is a benefit to blocking the NLRP3 inflammasome pathway in patients with sickle cell disease and other hemolytic conditions. However, a thorough understanding of the mechanisms of heme-induced inflammasome activation is needed to fully leverage this pathway for clinical benefit. This review will explore the mechanisms of heme-induced NLRP3 inflammasome activation and the role of this pathway in hemolytic conditions including sickle cell disease.

Keywords

Humans, Inflammasomes, NLR Family, Pyrin Domain-Containing 3 Protein, Heme, Hemolysis, Inflammation, Anemia, Sickle Cell, Interleukin-1beta, 10.1016/j.trsl.2022.08.011

Published Open-Access

yes

Recommended Citation

Salgar, Suruchi; Bolívar, Beatriz E; Flanagan, Jonathan M; et al., "The NLRP3 Inflammasome Fires Up Heme-Induced Inflammation in Hemolytic Conditions" (2023). Faculty and Staff Publications. 4910.
https://digitalcommons.library.tmc.edu/baylor_docs/4910