Inflammasomes and Fibrosis

Front Immunol. 2021 Jun 11:12:643149. doi: 10.3389/fimmu.2021.643149. eCollection 2021.

Abstract

Fibrosis is the final common pathway of inflammatory diseases in various organs. The inflammasomes play an important role in the progression of fibrosis as innate immune receptors. There are four main members of the inflammasomes, such as NOD-like receptor protein 1 (NLRP1), NOD-like receptor protein 3 (NLRP3), NOD-like receptor C4 (NLRC4), and absent in melanoma 2 (AIM2), among which NLRP3 inflammasome is the most studied. NLRP3 inflammasome is typically composed of NLRP3, ASC and pro-caspase-1. The activation of inflammasome involves both "classical" and "non-classical" pathways and the former pathway is better understood. The "classical" activation pathway of inflammasome is that the backbone protein is activated by endogenous/exogenous stimulation, leading to inflammasome assembly. After the formation of "classic" inflammasome, pro-caspase-1 could self-activate. Caspase-1 cleaves cytokine precursors into mature cytokines, which are secreted extracellularly. At present, the "non-classical" activation pathway of inflammasome has not formed a unified model for activation process. This article reviews the role of NLRP1, NLRP3, NLRC4, AIM2 inflammasome, Caspase-1, IL-1β, IL-18 and IL-33 in the fibrogenesis.

Keywords: IL-1β; NLRP3; caspase-1; fibrosis; inflammasome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • CARD Signaling Adaptor Proteins / physiology
  • Calcium-Binding Proteins / physiology
  • Caspase 1 / physiology
  • Fibrosis / etiology*
  • Humans
  • Inflammasomes / classification
  • Inflammasomes / physiology*
  • Interleukin-1beta / physiology
  • Interleukin-33 / physiology
  • Kidney / pathology
  • Liver Cirrhosis / etiology
  • Myocardium / pathology
  • NLR Family, Pyrin Domain-Containing 3 Protein / physiology
  • NLR Proteins / physiology
  • Pulmonary Fibrosis / etiology

Substances

  • CARD Signaling Adaptor Proteins
  • Calcium-Binding Proteins
  • Inflammasomes
  • Interleukin-1beta
  • Interleukin-33
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLR Proteins
  • NLRC4 protein, human
  • NLRP1 protein, human
  • Caspase 1