Inflammasomes in cancer: a double-edged sword

Kolb, Ryan; Liu, Guanghui; Janowski, Ann M.; Sutterwala, Fayyaz S.; Zhang, Weizhou

doi:10.1007/s13238-013-3051-8

Cited by 41 publications

(58 citation statements)

References 90 publications

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“…20 In the current study, γ-PGA showed antiinflammasome activity, which increases its potential as a promising target for cancer therapy and metabolic diseases. 13,14 Indeed, treatments targeting IL-1β (IL-1 receptor antagonist or IL-1β monoclonal antibodies), caspase-1 inhibitors or inflammasome inhibitors have been shown to control inflammasome-mediated diseases. 15,30 However, these diseases require continuous treatment because their symptoms manifest slowly, which furthers the physical and economic burden for patients.…”

Section: Discussionmentioning

confidence: 99%

“…13 Collectively, inflammasomes have received increased attention as new therapeutic targets of tumors and metabolic disorders. 14,15 In this study, we investigated the effects of γ-PGA on inflammasome activation. γ-PGA attenuated IL-1β and IL-18 secretion, which are readouts of inflammasome activation, in the presence of NLRP3, NLRC4 and AIM2 triggers.…”

Section: Introductionmentioning

confidence: 99%

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Poly-gamma-glutamic acid from Bacillus subtilis upregulates pro-inflammatory cytokines while inhibiting NLRP3, NLRC4 and AIM2 inflammasome activation

et al. 2016

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Poly-gamma-glutamic acid (γ-PGA) is a natural, edible and non-toxic polymer synthesized by Bacillus subtilis and is suggested as a safe biomaterial for the use in hydrogels and vaccine adjuvants. However, the effect of γ-PGA on inflammasome activation has not yet been studied in macrophages. Inflammasomes, which are intracellular multi-protein complexes, promote acute and chronic inflammation via interleukin-1β or interleukin-18 maturation, and they are known targets for metabolic syndromes and cancer. In this study, we observed that γ-PGA attenuated NLRP3, NLRC4 and AIM2 inflammasome activation, whereas it upregulated pro-inflammatory cytokine expression in human and murine macrophages. Although γ-PGA had conflicting effects on cytokine production and maturation, it clearly alleviated the severity of lipopolysaccharide-induced endotoxin shock in an animal model. Thus, we suggest γ-PGA as a candidate to control inflammasome-mediated disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Poly-gamma-glutamic acid from Bacillus subtilis upregulates pro-inflammatory cytokines while inhibiting NLRP3, NLRC4 and AIM2 inflammasome activation

et al. 2016

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“…However, excessive or inappropriate activation of NLRP3 inflammasome is implicated in the pathogenesis of inherited and acquired inflammatory diseases, leading to increased inflammatory responses in lung metastases and suppression of antitumor immunity in certain conditions . The NLRP3 inflammasome also plays an important role in the development and progression of gastrointestinal cancer, skin cancer, breast cancer and hepatocellular carcinoma . Furthermore, the over‐expressed and constitutively activated NLRP3 inflammasome contributes to the progression of late‐stage melanoma, whereas it is considerably down‐regulated in human hepatocellular carcinoma …”

Section: Nlrp3 Inflammasome and Tumorigenesismentioning

confidence: 99%

Differential role of the NLRP3 inflammasome in infection and tumorigenesis

Tartey

Kanneganti

2019

Immunology

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Dysregulated inflammation is one of the hallmarks of cancer initiation and progression. Emerging evidence indicates that inflammasomes play a central role in regulating immune cell functions in various infections and cancer. Inflammasomes are multimeric complexes consisting of nucleotide-binding oligomerization domain (NOD) -like receptors (NLRs). Among the NLRs, NOD1, NOD2 and NLRP3 respond to a variety of endogenous (i.e. damage-associated molecular patterns) and exogenous (i.e. pathogen-associated molecular patterns) stimuli. The NLRP3 inflammasome is associated with the onset and progression of autoinflammatory and autoimmune diseases, including metabolic disorders, multiple sclerosis, inflammatory bowel disease, and cryopyrin-associated periodic fever syndrome. NLRP3 is also associated with a wide variety of infections and tumorigenesis that are closely correlated with chemotherapy response and prognosis. In this review, we explore the rapidly expanding body of research on the expression and functions of NLRP3 in infections and cancers and outline novel inhibitors targeting the NLRP3 inflammasome that could be developed as therapeutic alternatives to current anticancer treatment.

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“…Mounting evidence indicates that NLRP3 inflammasome plays an important role in the development and progression of gastrointestinal cancer, skin cancer, breast cancer and hepatocellular carcinoma (7). However, the effects of NLRP3 inflammasome on the progression of various cancers are complex.…”

Section: Introductionmentioning

confidence: 99%

Activation of NLRP3 inflammasome enhances the proliferation and migration of A549 lung cancer cells

et al. 2016

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Lung cancer is the leading cause of cancer death, and it is widely accepted that chronic inflammation is an important risk for the development of lung cancer. Now, it is recognized that the nucleotide-binding and oligomerization domain (NOD) like receptors (NLRs)-containing inflammasomes are involved in cancer-related inflammation. This study was designed to investigate the effects of NLR family pyrin domain containing protein 3 (NLRP3) inflammasome on the proliferation and migration of lung adenocarcinoma cell line A549. Using 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay, scratch assay, and Transwell migration assay, we showed that activation of the NLRP3 inflammasome by LPS+ATP enhanced the proliferation and migration of A549 cells. Western blot analysis showed that activation of phosphorylation of Akt, ERK1/2, CREB and the expression of Snail increased, while the expression of E-cadherin decreased after the activation of NLRP3 inflammasome. Moreover, these effects were inhibited by the following treatments: i) downregulating the expression of NLRP3 by short hairpin RNA (shRNA) interference, ii) inhibiting the activation of NLRP3 inflammasome with a caspase-1 inhibitor, iii) blocking the interleukin-1β (IL-1β) and IL-18 signal transduction with IL-1 receptor antagonist (IL-1Ra) and IL-18 binding protein (IL-18BP). Collectively, these results indicate that NLRP3 inflammasome plays a vital role in regulating the proliferation and migration of A549 cells and it might be a potential target for the treatment of lung cancer.

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Inflammasomes in cancer: a double-edged sword

Cited by 41 publications

References 90 publications

Poly-gamma-glutamic acid from Bacillus subtilis upregulates pro-inflammatory cytokines while inhibiting NLRP3, NLRC4 and AIM2 inflammasome activation

Poly-gamma-glutamic acid from Bacillus subtilis upregulates pro-inflammatory cytokines while inhibiting NLRP3, NLRC4 and AIM2 inflammasome activation

Differential role of the NLRP3 inflammasome in infection and tumorigenesis

Activation of NLRP3 inflammasome enhances the proliferation and migration of A549 lung cancer cells

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