NLRP3 deletion inhibits inflammation-driven mouse lung tumorigenesis induced by benzo(a)pyrene and lipopolysaccharide

Huang, Li; Duan, Shuyin; Shao, Hua; Zhang, Aihua; Chen, Shuang; Zhang, Peng; Wang, Na; Wang, Wei; Wu, Yongjun; Wang, Jing; Liu, Hong; Yao, Wu; Qiao, Zhihua; Feng, Feifei

doi:10.1186/s12931-019-0983-4

Cited by 37 publications

(23 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Helicobacter pylori , hepatitis B or C, Epstein-Barr virus, and other infections are associated with increased cancer risk and carcinogenesis ( Moss & Blaser, 2005 ). In a mouse model benzo( a )pyrene (BaP) and lipopolysaccharide (LPS) promote lung tumorigenesis ( Huang et al, 2019 ). Multiple liver infections including liver fluke and Clonorchis sinensis administered with NDMA cause experimental cholangiocarcinoma ( Kim, Bae, Choi, & Hong, 2019 ; Laothong et al, 2013 ).…”

Section: Carcinogenesis Is a Multi-stage Multi-mechanism Processmentioning

confidence: 99%

Carcinogenesis: Failure of resolution of inflammation?

Fishbein

Hammock

Serhan

et al. 2021

Pharmacology & Therapeutics

138

View full text Add to dashboard Cite

Inflammation in the tumor microenvironment is a hallmark of cancer and is recognized as a key characteristic of carcinogens. However, the failure of resolution of inflammation in cancer is only recently being understood. Products of arachidonic acid and related fatty acid metabolism called eicosanoids, including prostaglandins, leukotrienes, lipoxins, and epoxyeicosanoids, critically regulate inflammation, as well as its resolution. The resolution of inflammation is now appreciated to be an active biochemical process regulated by endogenous specialized pro-resolving lipid autacoid mediators which combat infections and stimulate tissue repair/regeneration. Environmental and chemical human carcinogens, including aflatoxins, asbestos, nitrosamines, alcohol, and tobacco, induce tumor-promoting inflammation and can disrupt the resolution of inflammation contributing to a devastating global cancer burden. While mechanisms of carcinogenesis have focused on genotoxic activity to induce mutations, nongenotoxic mechanisms such as inflammation and oxidative stress promote genotoxicity, proliferation, and mutations. Moreover, carcinogens initiate oxidative stress to synergize with inflammation and DNA damage to fuel a vicious feedback loop of cell death, tissue damage, and carcinogenesis. In contrast, stimulation of resolution of inflammation may prevent carcinogenesis by clearance of cellular debris via macrophage phagocytosis and inhibition of an eicosanoid/cytokine storm of pro-inflammatory mediators. Controlling the host inflammatory response and its resolution in carcinogen-induced cancers will be critical to reducing carcinogen-induced morbidity and mortality. Here we review the recent evidence that stimulation of resolution of inflammation, including pro-resolution lipid mediators and soluble epoxide hydrolase inhibitors, may be a new chemopreventive approach to prevent carcinogen-induced cancer that should be evaluated in humans.

show abstract

Section: Carcinogenesis Is a Multi-stage Multi-mechanism Processmentioning

confidence: 99%

Carcinogenesis: Failure of resolution of inflammation?

Fishbein

Hammock

Serhan

et al. 2021

Pharmacology & Therapeutics

138

View full text Add to dashboard Cite

show abstract

“…In our previous study, we investigated the role of NLRP3 in mouse in ammation-related lung cancer initiation, and found that NLRP3 deletion inhibited lung cancer initiation induced by B(a)p or B(a)p plus LPS [7], we also found that NLRP3 in ammasome activation played an important role in B(a)p plus LPSinduced in ammation-related lung tumorigenesis in mice [8].…”

Section: Introductionmentioning

confidence: 88%

“…2 As an important and most investigated inflammatory regulator, NLRP3 inflammasome has been reported to have a key function in the occurrence of lung carcinoma, and recently studies show that inflammasomes may serve as preventing and treating cancer. 3,4 In our previous articles, we investigated the function of NLRP3 in inflammation-related lung carcinoma initiation, and found that the lack of NLRP3 inhibited B(a)p or B(a)p/LPS-related lung carcinoma initiation, 5 we also revealed that activated NLRP3 inflammasome could act on in lung cancer initiation in inflammation-related mice caused by B(a)p/LPS. 6 Glyburide, a NLRP3 inhibitor, plays an anti-inflammatory role to inhibit the NLRP3 inflammasome, decreases the production of proinflammatory cytokines, reduces the recruitment and migration of inflammatory cells, and production of nitricoxide.…”

Section: Introductionmentioning

confidence: 93%

Glyburide attenuates B(a)p and LPS‐induced inflammation‐related lung tumorigenesis in mice

Liu

Shao

et al. 2021

Environmental Toxicology

Self Cite

View full text Add to dashboard Cite

Glyburide (Gly) could inhibit NLRP3 inflammasome, as well as could be treated with Type 2 diabetes as a common medication. Despite more and more studies show that Gly could influence cancer risk and tumor growth, it remains unclear about the effect of Gly in lung tumorigenesis. To evaluate whether Gly inhibited lung tumorigenesis and explore the possible mechanisms, a benzo(a)pyrene [B(a)p] plus lipopolysaccharide (LPS)-induced non-diabetes mice model was established with B(a)p for 4 weeks and once a week (1 mg/mouse), then instilled with LPS for 15 weeks and once every 3 weeks (2.5 μg/ mouse) intratracheally. Subsequently, Gly was administered by gavage (10 μl/g body weight) 1 week before B(a)p were given to the mice until the animal model finished (when Gly was first given named Week 0). At the end of the experiment called Week 34, we analyzed the incidence, number and histopathology of lung tumors, and detected the expression of NLRP3, IL-1β, and Cleaved-IL-1β protein. We found that vehicles and tricaprylin+Gly could not cause lung carcinogenesis in the whole process. While the incidence and mean tumor count of mice in B(a)P/LPS+Gly group were decreased compared with B(a)p/LPS group. Moreover, Gly could alleviate inflammatory changes and reduce pathological tumor nest numbers compared with mice administrated with B(a)p/ LPS in histopathological examination. The B(a)p/LPS increased the expression of NLRP3, IL-1β, and Cleaved-IL-1β protein significantly than Vehicle, whereas decreased in B(a)P/ LPS+Gly (0.96 mg/kg) group compared with B(a)p/LPS group. Results suggested glyburide might inhibit NLRP3 inflammasome to attenuate inflammation-related lung tumorigenesis caused by intratracheal instillation of B(a)p/LPS in non-diabetes mice.

show abstract

“…Overexpression of IL-1β in lung adenocarcinoma (ADC) cells results in the promotion of experimental lung metastasis via enhanced expression of adhesion-, invasion- and angiogenesis-related molecules [ 76 ]. In line with this, NLRP3 promotes the mouse lung tumorigenesis induced by benzo(a)pyrene and LPS [ 77 ] and favors experimental lung metastasis development by affecting the ability of host NK cells to control the tumor [ 78 ]. Polydatin, a natural component, suppresses the proliferation and migration of NSCLC cells via the NF-κB pathway, inhibiting NLRP3 inflammasome activation [ 136 , 137 ].…”

Section: Role Of the Nlrp3 Inflammasome In Cancermentioning

confidence: 99%

Targeting the NLRP3 Inflammasome as a New Therapeutic Option for Overcoming Cancer

Missiroli

Perrone

Boncompagni

et al. 2021

Cancers

View full text Add to dashboard Cite

Inflammasomes are multiprotein complexes that regulate the maturation and secretion of the proinflammatory cytokines interleukin-1beta (IL-1βand interleukin-18 (IL-18) in response to various intracellular stimuli. As a member of the inflammasomes family, NLRP3 is the most studied and best characterized inflammasome and has been shown to be involved in several pathologies. Recent findings have made it increasingly apparent that the NLRP3 inflammasome may also play a central role in tumorigenesis, and it has attracted attention as a potential anticancer therapy target. In this review, we discuss the role of NLRP3 in the development and progression of cancer, offering a detailed summary of NLRP3 inflammasome activation (and inhibition) in the pathogenesis of various forms of cancer. Moreover, we focus on the therapeutic potential of targeting NLRP3 for cancer therapy, emphasizing how understanding NLRP3 inflammasome-dependent cancer mechanisms might guide the development of new drugs that target the inflammatory response of tumor-associated cells.

show abstract

NLRP3 deletion inhibits inflammation-driven mouse lung tumorigenesis induced by benzo(a)pyrene and lipopolysaccharide

Cited by 37 publications

References 30 publications

Carcinogenesis: Failure of resolution of inflammation?

Carcinogenesis: Failure of resolution of inflammation?

Glyburide attenuates B(a)p and LPS‐induced inflammation‐related lung tumorigenesis in mice

Targeting the NLRP3 Inflammasome as a New Therapeutic Option for Overcoming Cancer

Contact Info

Product

Resources

About