The potential role of interleukin-37 in infectious diseases

Allam, Gamal; Gaber, Asmaa; Othman, Sarah I.; Abdel-Moneim, Adel

doi:10.1080/08830185.2019.1677644

Cited by 21 publications

(12 citation statements)

References 69 publications

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“…In recent years, changes in the expression levels of various cytokines have become a hot topic in tumor immunology research. IL-37 is not only an inflammatory inhibitor but also an inhibitor of inherent inflammatory and immune responses (36), and it may play a role in inhibiting tumor growth in the tumor microenvironment (37). It was reported the elevated serum levels of interleukin-37 was correlated with poor prognosis in gastric cancer (38).…”

Section: Discussionmentioning

confidence: 99%

IL-37 Confers Anti-Tumor Activity by Regulation of m6A Methylation

Zhao

Chen

et al. 2021

Front. Oncol.

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N6-methyladenosine (m6A) is a common transcriptomic modification in cancer. Recently, it has been found to be involved in the regulation of non-small cell lung cancer (NSCLC) formation and metastasis. Interleukin 37 (IL-37) plays a crucial protective role in lung cancer. In our previous studies, we found that IL-37 is a potential novel tumor suppressor by inhibiting IL-6 expression to suppress STAT3 activation and decreasing epithelial-to-mesenchymal transition. Moreover, we found that treatment of IL-37 in lung cancer cells induced widespread and dynamic RNA m6A methylation. The effects of RNA m6A methylation of IL-37 treatment require further study. However, the functions of RNA m6A methylation of IL-37 treatment still await elucidation. Using MeRIP-seq and RNA-seq, we uncovered a unique m6A methylation profile in the treatment of IL-37 on the A549 cell line. We also showed the expression of m6A writers METTL3, METTL14, and WTAP and erasers ALKBH5 and FTO in A549 cells and lung cancer tissues after the treatment of IL-37. This study showed that IL-37 could lead to changes in m6A methylation level and related molecule expression level in A546 cells and may downregulate the proliferation by inhibiting Wnt5a/5b pathway in A549 cells. We conclude that IL-37 suppresses tumor growth through regulation of RNA m6A methylation in lung cancer cells.

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Section: Discussionmentioning

confidence: 99%

IL-37 Confers Anti-Tumor Activity by Regulation of m6A Methylation

Zhao

Chen

et al. 2021

Front. Oncol.

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“…Regarding this point, IL-37 has been considered a key player in a variety of inflammatory and autoimmune diseases (for instance, inflammatory respiratory diseases, inflammatory bowel diseases, rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriasis and multiple sclerosis), and studies have shown dysregulated expression of IL-37 under these conditions [15] , [16] . Besides, IL-37 has been reported to have important role in immunity against various infectious agents, including viruses, bacteria and fungi [17] . In COVID-19 patients, a significant association between IL-37 plasma levels and a clinical prognosis has been recently been identified.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-37 is down-regulated in serum of patients with severe coronavirus disease 2019 (COVID-19)

Ahmed

Ad’hiah

2021

Cytokine

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Pro-inflammatory and anti-inflammatory cytokines are indicated to play a prominent role in mediating the immunopathogenesis of coronavirus disease 19 (COVID-19). Interleukin (IL-37) is one of the anti-inflammatory cytokines that has been proposed to be involved in disease progression but the data are not overwhelming. Therefore, a case-control study was performed to analyze IL-37 levels in serum of 100 patients with severe COVID-19 and 100 blood donors (control group). Median age was significantly higher in COVID-19 cases than in controls. Stratification by gender, body mass index and ABO and Rh blood group systems showed no significant differences between patients and controls. Chronic diseases (cardiovascular and diabetes) were observed in 57.0% of patients. Serum levels of IL-37 and vitamin D were significantly decreased in patients compared to controls. The low level of IL-37 was more pronounced in males, overweight/obese cases, blood group B or AB cases, Rh-positive cases, and cases with no chronic disease. Low producers of IL-37 were more likely to develop COVID-19 (odds ratio = 2.66; 95% confidence interval = 1.51–4.70; corrected probability = 0.015). Receiver operating characteristic curve analysis demonstrated that a low serum level of IL-37 was a good predictor of COVID-19. Spearman's rank correlation analysis showed that IL-37 and vitamin D were significantly correlated. In conclusion, IL-37 was down-regulated in serum of patients with severe COVID-19 compared to controls. This down-regulation may be associated with an increased risk of disease. Gender, body mass index, blood groups and chronic disease status may also affect IL-37 levels.

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“…Although cytokines have been implicated in initiating anti-viral immune responses and involved in virus-mediated pathogenesis, host genetic variations may influence their responses to respiratory viral infections (Forbester and Humphreys, 2020). Among these cytokines is IL-37 and its immunological role in viral, bacterial and fungal infections has received increasing attention (Allam et al, 2020). Besides, accumulating data indicated that SNPs of IL37 gene are conserved among humans by selective force, and their potential involvement in the regulation of immune responses and susceptibility to human diseases has been proposed (Kang et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…Because of this immune function, IL-37 has been indicated to play a key role in the pathogenesis of a variety of inflammatory and autoimmune diseases, and in fact, dysregulated expression of IL-37 has been reported under these conditions (Ding et al, 2018;Wang et al, 2018). Besides, the antiviral, anti-bacterial and anti-fungal properties of IL-37 have also been recognized (Allam et al, 2020). With respect to COVID-19, IL-37 plasma levels have been significantly associated with the clinical prognosis of disease, and it has been predicted that severe illness can occur due to the lack of an IL-37-mediated response (Li et al, 2021).…”

Section: Introductionmentioning

confidence: 99%