The Crucial Role of NLRP3 Inflammasome in Viral Infection-Associated Fibrosing Interstitial Lung Diseases

Effendi, Wiwin Is; Nagano, Tatsuya

doi:10.3390/ijms221910447

Cited by 12 publications

(8 citation statements)

References 122 publications

(152 reference statements)

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“…Later, investigators found that inflammation is involved in different stages of IPF development due to the activation of the innate and adaptive immune systems [6][7][8]. Environmental influences and genetic risk factors leading to chronic inflammation may be associated with the development of IPF [9]. C-reactive protein (CRP) is often considered a marker of the inflammatory response in the acute phase.…”

Section: Introductionmentioning

confidence: 99%

Genetic association of circulating C-reactive protein levels with idiopathic pulmonary fibrosis: a two-sample Mendelian randomization study

Zhang

Zhou

et al. 2023

Respir Res

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Background Several observational studies have found that idiopathic pulmonary fibrosis (IPF) is often accompanied by elevated circulating C-reactive protein (CRP) levels. However, the causal relationship between them remains to be determined. Therefore, our study aimed to explore the causal effect of circulating CRP levels on IPF risk by the two-sample Mendelian randomization (MR) analysis. Methods We analyzed the data from two genome-wide association studies (GWAS) of European ancestry, including circulating CRP levels (204,402 individuals) and IPF (1028 cases and 196,986 controls). We primarily used inverse variance weighted (IVW) to assess the causal effect of circulating CRP levels on IPF risk. MR-Egger regression and MR-PRESSO global test were used to determine pleiotropy. Heterogeneity was examined with Cochran's Q test. The leave-one-out analysis tested the robustness of the results. Results We obtained 54 SNPs as instrumental variables (IVs) for circulating CRP levels, and these IVs had no significant horizontal pleiotropy, heterogeneity, or bias. MR analysis revealed a causal effect between elevated circulating CRP levels and increased risk of IPF (ORIVW = 1.446, 95% CI 1.128–1.854, P = 0.004). Conclusions The present study indicated that elevated circulating CRP levels could increase the risk of developing IPF in people of European ancestry.

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Section: Introductionmentioning

confidence: 99%

Genetic association of circulating C-reactive protein levels with idiopathic pulmonary fibrosis: a two-sample Mendelian randomization study

Zhang

Zhou

et al. 2023

Respir Res

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“…As a core protein, activated NLRP3 recruits the downstream proteins ASC and procaspase-1 to cause maturation and secretion of the highly proinflammatory cytokines IL-1β and IL-18 [35]. NLRP3 inflammasome activation is also observed in pulmonary fibrosis models induced by asbestos, silica and bleomycin, and pulmonary fibrosis is alleviated by the inhibition of NLRP3 inflammasome activation [36][37][38]. Our results are in agreement with the results of previous studies, showing that NecroX-5 significantly inhibited NLRP3 inflammasome activation in vivo and in vitro.…”

Section: Discussionmentioning

confidence: 99%

NecroX-5 ameliorates bleomycin-induced pulmonary fibrosis via inhibiting NLRP3-mediated epithelial–mesenchymal transition

Shu-Li

Yuan

et al. 2022

Respir Res

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Background Pulmonary fibrosis is a progressive and usually lethal pulmonary disease. Despite considerable research efforts, no effective therapeutic strategy for pulmonary fibrosis has been developed. NecroX-5 has been reported to possess anti-inflammatory, anti-oxidative and anti-tumor activities. In the present study, we aimed to determine whether NecroX-5 exhibits antifibrotic property in bleomycin (BLM)-induced pulmonary fibrosis. Results We found that pre-treatment with NecroX-5 alleviated inflammatory response, reduced oxidative stress, inhibited epithelial–mesenchymal transition (EMT), and ameliorated pulmonary fibrosis in vivo and in vitro. Our data further indicated that NecroX-5 substantially reduced activation of NLRP3 inflammasome and TGF-β1/Smad2/3 signaling in vivo and in vitro. Additionally, NLRP3 overexpression significantly reversed the protective effects of NecroX-5 in lung epithelial cells exposed to BLM. Conclusions Overall, our results demonstrate the potent antifibrotic properties of NecroX-5 and its therapeutic potential for pulmonary fibrosis.

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“…For example, the activation of the NLRP3 inflammasome by integrating multiple cellular and molecular signaling implicates robust fibroblast proliferation with activation of myofibroblast, matrix deposition, and aberrant epithelial–mesenchymal function. And, the NLRP3 inflammasome may trigger the release of the proinflammatory cytokines such as interleukin (IL)-1β, IL-6, and IL-18 and initiate or exacerbate the HD ( 2 , 3 ). The rate of virus infection in the ILD-IPF is high ( 4 , 5 ).…”

Section: Introductionmentioning

confidence: 99%

Colchicine Is a Weapon for Managing the Heart Disease Among Interstitial Lung Disease With Viral Infection: Have We Found the Holy Grail?

Yeh

Hung

Lin

et al. 2022

Front. Cardiovasc. Med.

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BackgroundThis study investigated the effect of colchicine use on the risks of heart disease (HD), pericarditis, endocarditis, myocarditis, cardiomyopathy, cardiac arrhythmia, and cardiac failure in patients having interstitial lung disease (ILD) with virus infection (ILD cohort).MethodsWe retrospectively enrolled ILD cohort between 2000 and 2013 from the Longitudinal Health Insurance Database and divided them into colchicine users (n = 12,253) and colchicine non-users (n = 12,253) through propensity score matching. The event of interest was the diagnosis of HD. The incidence of HD was analyzed using multivariate Cox proportional hazards models between colchicine users and the comparison cohort after adjustment for age, sex, medication, comorbidities, and index date based on the time-dependent analysis.ResultsColchicine users had a significantly lower risk of HD (aHR = 0.87, 95% confidence interval (CI]) = 0.82–0.92) than did the colchicine non-user. For colchicine non-users as the reference, the aHR (95% CI) of the patients who received colchicine of 2–7, 8–30, 31–150, and > 150 days were 0.89 (0.81–0.98), 0.84 (0.76–0.94), 090 (0.80–0.99), and 0.83 (0.74–0.93), respectively; regardless of duration use, the lower risk of HD persisted in colchicine users. The cumulative incidence of HD in colchicine users was significantly lower than that in the colchicine non-users (log-rank p < 0.001).ConclusionThe addition of short-term or long-term colchicine to standard medical therapy may have benefits to prevent the HD among the ILD patients concurrent with a virus infection or comorbidities even in elderly patients.

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The Crucial Role of NLRP3 Inflammasome in Viral Infection-Associated Fibrosing Interstitial Lung Diseases

Cited by 12 publications

References 122 publications

Genetic association of circulating C-reactive protein levels with idiopathic pulmonary fibrosis: a two-sample Mendelian randomization study

Genetic association of circulating C-reactive protein levels with idiopathic pulmonary fibrosis: a two-sample Mendelian randomization study

NecroX-5 ameliorates bleomycin-induced pulmonary fibrosis via inhibiting NLRP3-mediated epithelial–mesenchymal transition

Colchicine Is a Weapon for Managing the Heart Disease Among Interstitial Lung Disease With Viral Infection: Have We Found the Holy Grail?

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