Inflammasome as an Effective Platform for Fibrosis Therapy

Abstract

Fibrosis is the final stage of the development of chronic inflammation. It is characterized by excessive deposition of the extracellular matrix, leading to tissue structure damage and organ dysfunction, which is a serious threat to human health and life. However, the molecular mechanism of fibrosis is still unclear. Inflammasome is a molecular complex of proteins that has been becoming a key innate sensor for host immunity and is involved in pyroptosis, pathogen infection, metabolic syndrome, cellular stress, and tumor metastasis. Inflammasome signaling and downstream cytokine responses mediated by the inflammasome have been found to play an important role in fibrosis. The inflammasome regulates the secretion of IL-1β and IL-18, which are both critical for the process of fibrosis. Recently, researches on the function of inflammasome have attracted extensive attention, and data derived from these researches have increased our understanding of the effects and regulation of inflammasome during fibrosis. In this review, we emphasize the growing evidence for both indirect and direct effects of inflammasomes in triggering fibrosis as well as potential novel targets for antifibrotic therapies.

Polarization Behavior of Bone Macrophage as Well as Associated Osteoimmunity in Glucocorticoid-Induced Osteonecrosis of the Femoral Head

“…7 In the context of chronic inflammation, the necrotic bone continuously undergoes fibrosis repair, which hinders the reconstruction of normal bone structure and function. 8 Complex interactions existed between bone and immune cells (eg, macrophages, Th17 cells, and neutrophils). 9 Immune cells and their products could influence the activities of osteoclasts, osteoblasts, bone mesenchymal stem cells (BMSCs) and osteocytes, therefore coupling immune and skeletal systems.…”

“… 7 In the context of chronic inflammation, the necrotic bone continuously undergoes fibrosis repair, which hinders the reconstruction of normal bone structure and function. 8 …”

Regulatory Cues in Pulmonary Fibrosis—With Emphasis on the AIM2 Inflammasome

“…Inflammasome is a molecular complex of proteins that regulates the secretion of IL-1β and IL-18, both of which are critical for the fibrotic process. In recent years, research on the function of the inflammasome has attracted extensive attention [ 5 , 12 ]. In this review, we emphasize the direct and indirect roles of the AIM2 inflammasome in triggering fibrosis and explore potential novel targets for the treatment of PF.…”

The Dynamic Feature of Macrophage M1/M2 Imbalance Facilitates the Progression of Non-Traumatic Osteonecrosis of the Femoral Head

“…However, when the endogenous adverse stimuli persist or the normal homeostatic mechanisms cannot resolve the injury, chronic inflammation occurs at the site of injury ( Goodman and Maruyama, 2020 ; Newman et al, 2021 ). Chronic inflammation is detrimental to all tissues and organs, and it is a major driver of osteonecrosis ( Goodman and Maruyama, 2020 ; Chen et al, 2021 ). Within the chronic inflammatory microenvironment, the tissue continuously undergoes repair, thus local fibrosis occurs, which hinders the reconstruction of normal bone anatomy and function ( Goodman and Maruyama, 2020 ; Chen et al, 2021 ).…”

“…Chronic inflammation is detrimental to all tissues and organs, and it is a major driver of osteonecrosis ( Goodman and Maruyama, 2020 ; Chen et al, 2021 ). Within the chronic inflammatory microenvironment, the tissue continuously undergoes repair, thus local fibrosis occurs, which hinders the reconstruction of normal bone anatomy and function ( Goodman and Maruyama, 2020 ; Chen et al, 2021 ). NONFH is essentially a disorder of bone regeneration and repair following steroid or alcohol-induced bone injury.…”