Increased expression of ORMDL3 in allergic asthma: a case control and in vitro study

Nowakowska, Joanna; Olechnowicz, Anna; Langwiński, Wojciech; Koteluk, Oliwia; Lemańska, Żaneta; Jóźwiak, Kacper; Kamiński, Kacper; Łosiewski, Wojciech; Stegmayr, John; Wagner, Darcy E.; Alsafadi, Hani N.; Lindstedt, Sandra; Dziuba, Maria; Bielicka, Antonina; Graczyk, Zuzanna; Szczepankiewicz, Aleksandra

doi:10.1080/02770903.2022.2056896

Cited by 3 publications

(3 citation statements)

References 41 publications

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“…19,20 It can promote autophagy in human bronchial epithelium to influence asthma. [21][22][23] Consistent with our findings, a case-control study conducted by Hu et al 24 found the SNPs located at the intron of ORMDL3 might be the causal variants contributing to cervical cancer risk in the Han Chinese population. The specific roles of immune cells may differ depending on the stage of the disease, such as during early tumor formation, metastatic transmission and therapeutic intervention.…”

Section: Discussionsupporting

confidence: 91%

“…ORMDL3 is an endoplasmic reticulum membrane protein, which plays an important role in several processes, including oxidative stress, inflammation, negative regulation of the B‐cell apoptotic process, negative regulation of ceramide biosynthetic process, and sphingolipid metabolism 19,20 . It can promote autophagy in human bronchial epithelium to influence asthma 21–23 . Consistent with our findings, a case–control study conducted by Hu et al 24 found the SNPs located at the intron of ORMDL3 might be the causal variants contributing to cervical cancer risk in the Han Chinese population.…”

Section: Discussionsupporting

confidence: 88%

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Revealing genes associated with cervical cancer in distinct immune cells: A comprehensive Mendelian randomization analysis

Li,

Yi,

Sun

et al. 2024

Intl Journal of Cancer

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Human papillomavirus can be contracted by sexually active women. However, only a small proportion of these infections persist and have the potential to progress into cervical cancers, indicating a significant involvement of the immune system in cervical cancer development. Despite this, our understanding of the precise contributions of genes from different immune cell types in cervical cancers remains limited. Therefore, the primary objective of our study was to investigate the potential causal relationships between specific immune cell genes and the development of cervical cancers. By accessing expression quantitative trait loci datasets of 14 distinct immune cell types and genome wide association study of cervical cancers, we employed the summary data‐based Mendelian randomization (SMR) along with multi‐single nucleotide polymorphism (SNP)‐based SMR to identify significant genes associated with cervical cancers. Colocalization analysis was further conducted to explore the shared genetic causality. A total of 10 genes across 11 immune cell types (26 significant gene‐trait associations) were found to be associated with cervical cancers after false discovery rate correction. Notably, the ORMDL3, BRK1 and HMGN1 gene expression levels showed significant association with cervical cancer in specific immune cell types, respectively. These associations were supported by strong evidence of colocalization analyses. Our study has identified several genes in different immune cells that were associated with cervical cancer. However, further research is necessary to confirm these findings and provide more comprehensive insights into the association between these gene expressions and cervical cancer risk.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 88%

Revealing genes associated with cervical cancer in distinct immune cells: A comprehensive Mendelian randomization analysis

Li,

Yi,

Sun

et al. 2024

Intl Journal of Cancer

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“…Previous studies have failed to validate the effect of ORMDL3 expression on RSV bronchiolitis and recurrent wheezing. Due to ethical prohibitions such as taking tissue from the patient's bronchoscopic alveolar lavage or lung biopsy, ORMDL3 can also appear in lymphocytes in addition to the lungs, and it is reported that the expression of ORMDL3mRNA increases in the blood and bronchial epithelium of asthma patients (Nowakowska et al, 2023), infection and ORMDL3 expression in animal asthma models (Lu et al, 2016;Yang et al, 2019). RSV may activate ORMDL3 gene promoter expression via interferon regulatory factor-3 (IRF-3) (Wang et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Histone acetylation regulates ORMDL3 expression‐mediated NLRP3 inflammasome overexpression during RSV‐allergic exacerbation mice

Cheng,

He,

Zhao

et al. 2023

Journal Cellular Physiology

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Whether respiratory syncytial virus (RSV) infection in early life may induce orosomucoid 1‐like protein 3 (ORMDL3) and lead to NOD‐like receptor protein 3 (NLRP3) inflammasome overexpression in asthma, which could be alleviated by the inhibition of HAT p300. First, we explored the relationship between RSV, ORMDL3, and recurrent wheezing in the future through clinical data of infants with RSV‐induced bronchiolitis. Then, we used bronchial epithelium transformed with Ad12‐SV40 2B (BEAS‐2B) and an asthmatic mouse model of repeated RSV infection and OVA sensitization and challenge (rRSV + OVA) in early life to assess the effects of ORMDL3 on NLRP3 inflammasome and that of histone acetylation on ORMDL3 regulation. ORMDL3 overexpression is the independent risk factor of recurrent wheezing in RSV‐bronchiolitis follow‐up. In BEAS‐2B, ORMDL3‐induced NLRP3 inflammasome expression. BEAS‐2B infected by RSV resulted in overexpression of ORMDL3 and NLRP3 inflammasome and histone hyperacetylation, while ORMDL3‐small interfering RNA and C646 interfered could decrease NLRP3 inflammasome. ORMDL3 overexpression in mouse lung increased NLRP3 inflammasome. The expression of ORMDL3 and NLRP3 inflammasome significantly increased, with histone hyperacetylation in the lung in rRSV + OVA mice. p300 and acetylH3 bound to ORMDL3 promoter. In C646 + rRSV + OVA mice, C646 alleviated lung inflammation and overexpression of ORMDL3 and NLRP3 inflammasome. RSV activated ORMDL3 overexpression through histone hyperacetylation and induced NLRP3 inflammasome expression.

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Allergy: Mechanistic insights into new methods of prevention and therapy

Akdiş

Boyd

et al. 2023

Sci. Transl. Med.

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In the past few decades, the prevalence of allergic diseases has increased worldwide. Here, we review the etiology and pathophysiology of allergic diseases, including the role of the epithelial barrier, the immune system, climate change, and pollutants. Our current understanding of the roles of early life and infancy; diverse diet; skin, respiratory, and gut barriers; and microbiome in building immune tolerance to common environmental allergens has led to changes in prevention guidelines. Recent developments on the mechanisms involved in allergic diseases have been translated to effective treatments, particularly in the past 5 years, with additional treatments now in advanced clinical trials.

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Increased expression of ORMDL3 in allergic asthma: a case control and in vitro study

Cited by 3 publications

References 41 publications

Revealing genes associated with cervical cancer in distinct immune cells: A comprehensive Mendelian randomization analysis

Revealing genes associated with cervical cancer in distinct immune cells: A comprehensive Mendelian randomization analysis

Histone acetylation regulates ORMDL3 expression‐mediated NLRP3 inflammasome overexpression during RSV‐allergic exacerbation mice

Allergy: Mechanistic insights into new methods of prevention and therapy

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