NLRP3 inflammasome expression in idiopathic pulmonary fibrosis and rheumatoid lung

Lasithiotaki, Ismini; Giannarakis, Ioannis; Tsitoura, Eliza; Samara, Katerina D.; Margaritopoulos, George; Choulaki, Christiana; Vasarmidi, Eirini; Tzanakis, Νikolaos; Voloudaki, Argyro; Sidiropoulos, Prodromos; Siafakas, Nikolaos M.; Αντωνίου, Κατερίνα

doi:10.1183/13993003.00564-2015

Cited by 106 publications

(74 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specifically, IL-18 protein levels were highly expressed in alveolar macrophages and epithelial cells [70]. Lasithiotaki et al showed that transcriptional levels of inflammasome components, NLRP3 and caspase-1, were elevated in IPF patients when compared to the controls [71]. In addition, NLRP3 inflammasome activation by ATP was significantly increased in alveolar macrophages from IPF patients when compared to the controls [71].…”

Section: The Role Of Inflammasome-dependent Inflammation In Ipfmentioning

confidence: 99%

DROSHA-Dependent miRNA and AIM2 Inflammasome Activation in Idiopathic Pulmonary Fibrosis

Cho

Lee

Stout‐Delgado

et al. 2020

IJMS

View full text Add to dashboard Cite

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease. Chronic lung inflammation is linked to the pathogenesis of IPF. DROSHA, a class 2 ribonuclease III enzyme, has an important role in the biogenesis of microRNA (miRNA). The function of miRNAs has been identified in the regulation of the target gene or protein related to inflammatory responses via degradation of mRNA or inhibition of translation. The absent-in-melanoma-2 (AIM2) inflammasome is critical for inflammatory responses against cytosolic double stranded DNA (dsDNA) from pathogen-associated molecular patterns (PAMPs) and self-DNA from danger-associated molecular patterns (DAMPs). The AIM2 inflammasome senses double strand DNA (dsDNA) and interacts with the adaptor apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which recruits pro-caspase-1 and regulates the maturation and secretion of interleukin (IL)-1β and IL-18. A recent study showed that inflammasome activation contributes to lung inflammation and fibrogenesis during IPF. In the current review, we discuss recent advances in our understanding of the DROSHA–miRNA–AIM2 inflammasome axis in the pathogenesis of IPF.

show abstract

Section: The Role Of Inflammasome-dependent Inflammation In Ipfmentioning

confidence: 99%

DROSHA-Dependent miRNA and AIM2 Inflammasome Activation in Idiopathic Pulmonary Fibrosis

Cho

Lee

Stout‐Delgado

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Recent studies suggest a role for nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3) inflammasome activation in lung inflammation and fibrosis (7)(8)(9)(10)(11). The NLRP3 inflammasome is a key signaling platform that is activated by a variety of signals, such as reactive oxygen species (ROS), to produce IL-1b and IL-18 (12).…”

Section: Clinical Relevancementioning

confidence: 99%

Age-Dependent Susceptibility to Pulmonary Fibrosis Is Associated with NLRP3 Inflammasome Activation

Stout‐Delgado

Cho

Chu

et al. 2016

Am J Respir Cell Mol Biol

118

105

View full text Add to dashboard Cite

Aging has been implicated in the development of pulmonary fibrosis, which has seen a sharp increase in incidence in those older than 50 years. Recent studies demonstrate a role for the nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3) inflammasome and its regulated cytokines in experimental lung fibrosis. In this study, we tested the hypothesis that age-related NLRP3 inflammasome activation is an important predisposing factor in the development of pulmonary fibrosis. Briefly, young and aged wild-type and NLRP3(-/-) mice were subjected to bleomycin-induced lung injury. Pulmonary fibrosis was determined by histology and hydroxyproline accumulation. Bone marrow and alveolar macrophages were isolated from these mice. NLRP3 inflammasome activation was assessed by co-immunoprecipitation experiments. IL-1β and IL-18 production was measured by ELISA. The current study demonstrated that aged wild-type mice developed more lung fibrosis and exhibited increased morbidity and mortality after bleomycin-induced lung injury, when compared with young mice. Bleomycin-exposed aged NLRP3(-/-) mice had reduced fibrosis compared with their wild-type age-matched counterparts. Bone marrow-derived and alveolar macrophages from aged mice displayed higher levels of NLRP3 inflammasome activation and caspase-1-dependent IL-1β and IL-18 production, which was associated with altered mitochondrial function and increased production of reactive oxygen species. Our study demonstrated that age-dependent increases in alveolar macrophage mitochondrial reactive oxygen species production and NLRP3 inflammasome activation contribute to the development of experimental fibrosis.

show abstract

“…NALP3 has been widely investigated with respect to immune response over the past several decades, and it is considered to act as a general sensor for cellular stress. In recent years, NALP3 has been found to play important roles in various pathological processes, including diabetes mellitus (22,23), non-alcoholic steatohepatitis (24,25), chronic kidney diseases (26) and IPF (27). Furthermore, an increasing volume of evidence indicates that NALP3 serves as an important factor in organ fibrosis.…”

Section: Discussionmentioning

confidence: 99%

The NALP3 inflammasome is required for collagen synthesis via the NF‑κB pathway

2018

View full text Add to dashboard Cite

The NALP3 inflammasome interacts with various immune and cell metabolic pathways and may participate in pulmonary fibrosis. However, little is known on its regulatory mechanism with respect to collagen synthesis. The objective of the present study was to investigate whether NALP3 inflammasome activation is involved in H2O2‑mediated collagen synthesis, in addition to examining the possible cell signaling mechanisms underlying this effect. It was demonstrated that the NF‑κB signaling pathway was activated under conditions of H2O2‑mediated oxidative stress in NIH‑3T3 mouse embryonic fibroblasts. H2O2‑exposed fibroblasts exhibited activated NALP3 inflammasomes via increased NALP3, apoptosis‑associated Speck‑like protein and caspase‑1 expression and the secretion of interleukin‑1β. H2O2 also elevated α‑SMA and type I collagen expression. In vitro silencing of NALP3 attenuated the degradation of IκBα and decreased the synthesis of type I collagen. Furthermore, the NALP3 inflammasome was found to be activated in bleomycin‑induced pulmonary fibrosis in mice, and this activation was relieved by a nuclear factor (NF)‑κB inhibitor. Taken together, these findings indicate that the NALP3 inflammasome is involved in H2O2‑induced type I collagen synthesis, which is mediated by the NF‑κB signaling pathway. Additionally, the NALP3 inflammasome contributes to the development of bleomycin‑induced pulmonary fibrosis.

show abstract

NLRP3 inflammasome expression in idiopathic pulmonary fibrosis and rheumatoid lung

Cited by 106 publications

References 40 publications

DROSHA-Dependent miRNA and AIM2 Inflammasome Activation in Idiopathic Pulmonary Fibrosis

DROSHA-Dependent miRNA and AIM2 Inflammasome Activation in Idiopathic Pulmonary Fibrosis

Age-Dependent Susceptibility to Pulmonary Fibrosis Is Associated with NLRP3 Inflammasome Activation

The NALP3 inflammasome is required for collagen synthesis via the NF‑κB pathway

Contact Info

Product

Resources

About