GSDMD-miR-223-NLRP3 axis involved in B(a)P-induced inflammatory injury of alveolar epithelial cells

Kong, Xianwen; Gao, Min; Liu, Yitong; Zhang, Peng; Li, Mengyuan; Ma, Pengwei; Shang, Pingping; Wang, Wei; Liu, Hong; Zhang, Qiao; Feng, Feifei

doi:10.1016/j.ecoenv.2022.113286

Cited by 20 publications

(4 citation statements)

References 39 publications

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“…A study suggests that melatonin exerts protective roles on LPS-induced ALI and pyroptosis by inhibiting the NLRP3-GSDMD pathway [ 28 ]. GSDMD may regulate NLRP3 inflammasome involved in Benzo(a)pyrene (B(a)P) induced inflammatory damage in alveolar epithelial cells (A549 cells) [ 29 ]. Honokiol (HKL) inhibits the expression levels of NLRP3, CASP1, and GSDMD and could attenuate the pathological injury in LPS-induced ALI rats [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Hydrogen on AM Pyroptosis Induced by Severe Burns in Rats

Luo

Lin

Zhang

et al. 2023

JPM

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Background: Hydrogen has anti-inflammatory and antioxidant effects and is beneficial to multiple organs. However, its effect on alveolar macrophage (AM) pyroptosis induced by burns is still unclear. The purpose of this research was to study the possible positive effects of hydrogen on burn-induced lung injury and the effects of hydrogen on AM pyroptosis during acute lung injury (ALI) induced by burns. Methods: In this study, histological changes in rat lungs in vivo were evaluated by micro-CT, and histological changes in isolated lungs were evaluated by hematoxylin and eosin (HE) staining. The expressions of leucine rich repeat (LRR) and pyrin domain (PYD) containing protein 3 (NLRP3), caspase-1 and Gasdermin-D (GSDMD) were analyzed by Western blotting. The expression of GSDMD was measured by immunofluorescence to evaluate the levels of lung inflammation and pyroptosis. The level of inflammation was assessed by enzyme-linked immunosorbent assay (ELISA). Pyroptosis was observed by transmission electron microscopy. Results: We observed that severe burn resulted in increased IL-1β and IL-18, overexpression of NLRP3 and caspase-1 proteins, and pyroptosis in rat lung tissues, as demonstrated by GSDMD overexpression and electron microscopy of AMs. We also observed that hydrogen treatment partially reversed the increase in lung tissue density and reduced pulmonary inflammation. Moreover, hydrogen reduced the HE pathological injury score in the lung tissues of severely burned rats. Hydrogen treatment significantly reduced the contents of IL-1β and IL-18 in the lung tissues and decreased the expression of NLRP3, caspase-1 and GSDMD proteins compared with the burn group. Transmission electron microscopy results also showed that the number of AM membrane pores was significantly reduced in the hydrogen treatment group. Conclusions: The results of this study suggest that hydrogen may protect against ALI induced by burn injury by inhibiting pyroptosis of macrophages via NLRP3.

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Section: Discussionmentioning

confidence: 99%

Effect of Hydrogen on AM Pyroptosis Induced by Severe Burns in Rats

Luo

Lin

Zhang

et al. 2023

JPM

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“…In lung epithelial cells, upregulation of miR-223 by STIM1 can alleviate influenza A virus induced inflammatory injury in lung epithelial cells by deactivating NLRP3 and inflammasomes ( 55 ). Moreover, suppression of miR-223 in A549 cells induced by B(a)P resulted in elevated levels of TNF-α and IL-6 in the supernatant, as well as increased protein level of NLRP3, IL-1β, IL-18, caspase-1 ( 56 ). A recent study from Ren revealed that in animal models of dry eye (DE), miR-223 can suppress inflammation induced by hyperosmolarity in corneal epithelial cells by reducing the activation of NLRP3.…”

Section: The Role Of Mir-223 In the Inflammatory Responsementioning

confidence: 99%

miR-223: a key regulator of pulmonary inflammation

Shi

Zhao

et al. 2023

Front. Med.

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Small noncoding RNAs, known as microRNAs (miRNAs), are vital for the regulation of diverse biological processes. miR-223, an evolutionarily conserved anti-inflammatory miRNA expressed in cells of the myeloid lineage, has been implicated in the regulation of monocyte–macrophage differentiation, proinflammatory responses, and the recruitment of neutrophils. The biological functions of this gene are regulated by its expression levels in cells or tissues. In this review, we first outline the regulatory role of miR-223 in granulocytes, macrophages, endothelial cells, epithelial cells and dendritic cells (DCs). Then, we summarize the possible role of miR-223 in chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), coronavirus disease 2019 (COVID-19) and other pulmonary inflammatory diseases to better understand the molecular regulatory networks in pulmonary inflammatory diseases.

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“…Meanwhile, several studies in recent years have shown that cytokines can be released from living cells without pyroptosis occurring in the process ( Gaidt et al, 2016 ; Zanoni et al, 2016 ). Interestingly, GSDMD may also regulate the NLRP3 inflammasome through miR-223 ( Kong et al, 2022 ). Furthermore, in the absence of GSDMD, sustained exposure to LPS can trigger pyroptosis and the release of inflammatory cytokines via activation of the caspase-3/GSDME axis.…”

Section: Nlrp3 Inflammosome Activation and Pyroptosismentioning

confidence: 99%

NLRP3-mediated pyroptosis in diabetic nephropathy

Wan

Pan

et al. 2022

Front. Pharmacol.

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Diabetic nephropathy (DN) is the main cause of end-stage renal disease (ESRD), which is characterized by a series of abnormal changes such as glomerulosclerosis, podocyte loss, renal tubular atrophy and excessive deposition of extracellular matrix. Simultaneously, the occurrence of inflammatory reaction can promote the aggravation of DN-induced kidney injury. The most important processes in the canonical inflammasome pathway are inflammasome activation and membrane pore formation mediated by gasdermin family. Converging studies shows that pyroptosis can occur in renal intrinsic cells and participate in the development of DN, and its activation mechanism involves a variety of signaling pathways. Meanwhile, the activation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome can not only lead to the occurrence of inflammatory response, but also induce pyroptosis. In addition, a number of drugs targeting pyroptosis-associated proteins have been shown to have potential for treating DN. Consequently, the pathogenesis of pyroptosis and several possible activation pathways of NLRP3 inflammasome were reviewed, and the potential drugs used to treat pyroptosis in DN were summarized in this review. Although relevant studies are still not thorough and comprehensive, these findings still have certain reference value for the understanding, treatment and prognosis of DN.

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GSDMD-miR-223-NLRP3 axis involved in B(a)P-induced inflammatory injury of alveolar epithelial cells

Cited by 20 publications

References 39 publications

Effect of Hydrogen on AM Pyroptosis Induced by Severe Burns in Rats

Effect of Hydrogen on AM Pyroptosis Induced by Severe Burns in Rats

miR-223: a key regulator of pulmonary inflammation

NLRP3-mediated pyroptosis in diabetic nephropathy

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