Interleukin-37: A Link Between COVID-19, Diabetes, and the Black Fungus

Tokajian, Sima; Merhi, Georgi; Khoury, Charbel Al; Nemer, Georges

doi:10.3389/fmicb.2021.788741

Cited by 6 publications

(7 citation statements)

References 75 publications

(86 reference statements)

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“…Qi reported that IL-37 improves in uenza pneumonia in vivo [23]. A recent study demonstrated that IL-37 alleviates systemic in ammation after a new coronavirus (COVID-19) infection, and low IL-37 plasma levels serve as a marker for the severity of the viral infection [24]. It also plays a bene cial role in CVD.…”

Section: Discussionmentioning

confidence: 99%

IL-37 reduces calcification by inhibiting the oxidized low-density lipoprotein(ox-LDL)-induced toll-like receptor(TLR)/nuclear factor kappa-B(NF-κB) signaling pathway and suppressing cellular osteogenic transformation in smooth muscle cells

CAO²,

Wang³

et al. 2022

Preprint

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[Objective] Cardiovascular disease (CVD) is one of the leading causes of high mortality worldwide, and vascular calcification (VC) increases the incidence of adverse prognostic events and mortality in CVD. Osteogenic transformation of vascular smooth muscle cells (VSMCs) and induction of inflammation could be among the mechanisms of VC. Interleukin 37 (IL-37) is an anti-inflammatory factor that protects against atherosclerosis (AS) and VC by unknown mechanisms. Thus, the present study aimed to investigate the effect and mechanism of IL-37 on calcification in human aortic smooth muscle cells (HASMCs). [Methods] The human aortic smooth muscle cells (HA-SMC) were purchased from CTCC (Meisen, China), Alizarin red S staining was used to measure the degree of cell calcification, flow cytometry measured the level of apoptosis, cell counting kit-8 (CCK-8) measured the cell proliferation activity, and qPCR was used to measure the expression of toll-like receptor(TLR4),nuclear factor kappa-B( NF-κB), Runt-related Transcription Factor 2(RUNX2), Smooth muscle actin(SMA), smooth muscle 22 alpha (SM22α), Msh homeobox 2(MSX2)、Osteocalcin(OC) and alkaline phosphatase (ALP). Western blot measured the level of TLR4, NF-κB, RUNX2, and phosphorylated NF-κB(PP65), and immunofluorescence was used to detect the expression and location of SM22α.Differences were analyzed via Student’s t test or one-way analysis of variance [Results] Ox-LDL induction caused HA-SMC calcification and promoted HA-SMC apoptosis and value addition. After IL-37 intervention, calcification was significantly reduced, TLR4/NF-κB/RUNX2 expression activated by ox-LDL was decreased, and cell proliferation activity was inhibited, apoptosis rate was decreased, and PP65 expression was downregulated. IL-37 inhibited P65phosphorylation by inhibiting TLR. Down-regulation of osteogenesis-related factor expression plays a protective role against cellular calcification. [Conclusion] The current data demonstrated that IL-37 inhibits NF-κB phosphorylation by downregulating the ox-LDL-activated TLR4-NF-κ Bsignaling pathway, reduces the expression of the osteogenic transcription factor RUNX2/ALP, and inhibits VSMC osteogenic transformation, thereby reducing the level of cellular calcification. These findings provided a basis for the use of IL-37 as a novel therapeutic target.

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Section: Discussionmentioning

confidence: 99%

IL-37 reduces calcification by inhibiting the oxidized low-density lipoprotein(ox-LDL)-induced toll-like receptor(TLR)/nuclear factor kappa-B(NF-κB) signaling pathway and suppressing cellular osteogenic transformation in smooth muscle cells

CAO²,

Wang³

et al. 2022

Preprint

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“…The challenge is how to accelerate a covid-19 identification while maintaining high precision. Like how it is difficult to manipulate COVID-19 data, which has intricate arrangements and large volumes, using human-dependent medical tools [27]. Figure 2 displays the information about applications for blockchain and AI technology.…”

Section: Blockchain Technology In Smart City Application Against Covi...mentioning

confidence: 99%

“…Blockchain technology is used by public and commercial (hired) agencies to address the problems of plagiarism and other forms of fake material on these sites. The European Centre for Disease Prevention and Control estimates that 10 million people are affected with this virus every year [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], making prevention efforts difficult due to a lack of available tools like immunizations and a COVID-19 protection package [21][22][23][24][25][26][27][28][29][30]. Numerous studies demonstrated that X-rays are crucial in the initial phases of diagnosis of the virus.…”

Section: Introductionmentioning

confidence: 99%

Investigation of Blockchain for COVID-19: A Systematic Review, Applications and Possible Challenges

Badshah¹,

Imad²,

Hassan³

et al. 2023

EAI Endorsed Trans Smart Cities

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Smart city is emerging application in which many Internet of Things (IoT) devices are embedded to perform overall monitoring and perform processing automatically. In smart city the authenticity is key problem and many users in the in smart city has faced challenges during COVID-19. The COVID-19 epidemic, a deadly virus, first appeared in the globe in 2019. The World Health Organization (WHO) states that it is almost certainly feasible to contain this virus in its early phases if some precautions are taken. To contain the infection, most nations declared emergencies both inside and outside their borders and prohibited travel. Artificial intelligence and blockchain are being used in smart city applications to monitor the general condition in the nation and reduce the mortality rate. Blockchain has also made it possible to safeguard patient medical histories and provide epidemic tracking. AI also offers the ideal, wanted answer for correctly identifying the signs. The primary goal of this study is to fully investigate blockchain technology and artificial intelligence (AI) in relation to COVID-19. A case study that was recently developed to identify and networked pathogens acquired important knowledge and data. Additionally, AI that can handle massive quantities of medical data and perform difficult jobs will be able to reduce the likelihood of intricacy in data analysis. Lastly, we highlight the present difficulties and suggest potential paths for addressing the 19 diseases in future circumstances.

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“…Besides, up‐regulated expression of IL‐37 has been associated with increased insulin sensitivity in elderly patients with T2DM 10 . A link between IL‐37 and a dysregulated immune response in COVID‐19 and diabetes has also recently been proposed 11 …”

Section: Introductionmentioning

confidence: 99%

“…10 A link between IL-37 and a dysregulated immune response in COVID-19 and diabetes has also recently been proposed. 11 IL-39, the latest discovered member of the IL-12 family of cytokines, is heterodimer glycoprotein composed of two covalently linked subunits, IL-23p19 and Epstein-Barr virus-induced gene (Ebi3). 12 In vitro and in vivo studies in mice revealed that IL-23p19 and Ebi3 are secreted by B cells upon stimulation with lipopolysaccharides (LPS).…”

mentioning

confidence: 99%

Interleukin‐39 is a novel cytokine associated with type 2 diabetes mellitus and positively correlated with body mass index

Nussrat

Ad’hiah

2023

Endocrino Diabet & Metabol

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Introduction It is suggested that cytokines play a key role in the pathogenesis of type 2 diabetes mellitus (T2DM). Therefore, this study explored two recently discovered cytokines, interleukin (IL)‐37 (anti‐inflammatory) and IL‐39 (pro‐inflammatory), in T2DM due to limited data in this context. Methods Serum IL‐37 and IL‐39 levels were determined in 106 T2DM patients and 109 controls using enzyme‐linked immunosorbent assay kits. Results Serum levels (median and interquartile range) of IL‐37 (79 [47–102] vs. 60 [46–89] ng/L; probability [p] = .04) and IL‐39 (66 [59–69] vs. 31 [19–42] ng/L; p < .001) were significantly elevated in T2DM patients compared to controls. As indicated by the area under the curve (AUC), IL‐39 (AUC = 0.973; p < .001) was more predictable for T2DM than IL‐37 (AUC = 0.582; p = .039). Elevated levels of IL‐39 were significantly associated with T2DM (odds ratio = 1.30; p < .001), while IL‐37 did not show this association. Classification of IL‐37 and IL‐39 levels by demographic and clinical characteristics of patients revealed some significant differences including gender (IL‐39), body mass index (BMI; IL‐37 and IL‐39) and diabetic neuropathy (IL‐39). BMI was positively correlated with IL‐39 (correlation coefficient [rs] = 0.27; p = .005) and glycosylated haemoglobin (rs = 0.31; p = .001), and negatively correlated with age at onset (rs = −0.24; p = .015). Conclusions IL‐37 and IL‐39 levels were elevated in the serum of T2DM patients. Besides, IL‐39 is proposed to be a novel cytokine associated with T2DM and positively correlated with BMI.

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Interleukin-37: A Link Between COVID-19, Diabetes, and the Black Fungus

Abstract: Graphical Abstract

Cited by 6 publications

References 75 publications

IL-37 reduces calcification by inhibiting the oxidized low-density lipoprotein(ox-LDL)-induced toll-like receptor(TLR)/nuclear factor kappa-B(NF-κB) signaling pathway and suppressing cellular osteogenic transformation in smooth muscle cells

IL-37 reduces calcification by inhibiting the oxidized low-density lipoprotein(ox-LDL)-induced toll-like receptor(TLR)/nuclear factor kappa-B(NF-κB) signaling pathway and suppressing cellular osteogenic transformation in smooth muscle cells

Investigation of Blockchain for COVID-19: A Systematic Review, Applications and Possible Challenges

Interleukin‐39 is a novel cytokine associated with type 2 diabetes mellitus and positively correlated with body mass index

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