Gene expressions changes in bronchial epithelial cells: Markers for respiratory sensitizers and exploration of the NRF2 pathway

Remy, Sylvie; Verstraelen, Sandra; Heuvel, Rosette Van Den; Nelissen, Inge; Lambrechts, Nathalie; Hooyberghs, Jef; Schoeters, Greet

doi:10.1016/j.tiv.2013.10.017

Cited by 14 publications

(8 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These suggested that UPP1 may involve in young sepsis patients. Recently, UPP1 also has been reported to play a pivotal role in inflammatory and immune biological processes such as respiratory allergy ( 31 ) and chronic atrophic gastritis ( 32 ). Thus, UPP1 may affect the occurrence and progression of pediatric sepsis shock by regulating inflammatory and immune responses.…”

Section: Discussionmentioning

confidence: 99%

Analysis of signature genes and association with immune cells infiltration in pediatric septic shock

et al. 2022

View full text Add to dashboard Cite

BackgroundEarly diagnosis of septic shock in children is critical for prognosis. This study committed to investigate the signature genes and their connection with immune cells in pediatric septic shock.MethodsWe screened a dataset of children with septic shock from the GEO database and analyzed differentially expressed genes (DEGs). Functional enrichment analysis was performed for these DEGs. Weighted gene co-expression network analysis (WCGNA) was used to screen the key modules. Least absolute shrinkage and selection operator (LASSO) and random forest analysis were finally applied to identify the signature genes. Then gene set enrichment analysis (GSEA) was exerted to explore the signaling pathways related to the hub genes. And the immune cells infiltration was subsequently classified via using CIBERSORT.ResultsA total of 534 DEGs were screened from GSE26440. The data then was clustered into 17 modules via WGCNA, which MEgrey module was significantly related to pediatric septic shock (cor=−0.62, p<0.0001). LASSO and random forest algorithms were applied to select the signature genes, containing UPP1, S100A9, KIF1B, S100A12, SLC26A8. The receiver operating characteristic curve (ROC) of these signature genes was 0.965, 0.977, 0.984, 0.991 and 0.989, respectively, which were verified in the external dataset from GSE13904. GSEA analysis showed these signature genes involve in positively correlated fructose and mannose metabolism and starch and sucrose metabolism signaling pathway. CIBERSORT suggested these signature genes may participate in immune cells infiltration.ConclusionUPP1, S100A9, KIF1B, S100A12, SLC26A8 emerge remarkable diagnostic performance in pediatric septic shock and involved in immune cells infiltration.

show abstract

Section: Discussionmentioning

confidence: 99%

Analysis of signature genes and association with immune cells infiltration in pediatric septic shock

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Lei Xue et al found that SLC16A3 has good prognostic significance in lung adenocarcinoma ( Xue et al, 2021 ). Recently, UPP1 was reported to play a vital role in immune and inflammatory biological process during particular events such as chronic atrophic gastritis ( Yang et al, 2020 ) and respiratory allergy ( Remy et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Neoantigens and Construction of Immune Subtypes in Prostate Adenocarcinoma

et al. 2022

View full text Add to dashboard Cite

Background: Messenger ribonucleic acid (mRNA) vaccine has been considered as a potential therapeutic strategy and the next research hotspot, but their efficacy against prostate adenocarcinoma (PRAD) remains undefined. This study aimed to find potential antigens of PRAD for mRNA vaccine development and identify suitable patients for vaccination through immunophenotyping.Methods: Gene expression profiles and clinical information were obtained from TCGA and ICGC. GEPIA2 was used to calculate the prognostic index of the selected antigens. The genetic alterations were compared on cBioPortal and the correlation between potential antigen and immune infiltrating cells was explored by TIMER. ConsensusClusterPlus was used to construct a consistency matrix, and identify the immune subtypes. Graph learning-based dimensional reduction was performed to depict immune landscape. Boruta algorithm and LASSO logistic analysis were used to screen PRAD patients who may benefit from mRNA vaccine.Results: Seven potential tumor antigens selected were signiﬁcantly positively associated with poor prognosis and the antigen-presenting immune cells (APCs) in PRAD, including ADA, FYN, HDC, NFKBIZ, RASSF4, SLC6A3, and UPP1. Five immune subtypes of PRAD were identified by differential molecular, cellular, and clinical characteristics in both cohorts. C3 and C5 had immune “hot” and immunosuppressive phenotype, On the contrary, C1&C2 had immune “cold” phenotype. Finally, the immune landscape characterization showed the immune heterogeneity among patients with PRAD.Conclusions: ADA, FYN, HDC, NFKBIZ, RASSF4, SLC6A3, and UPP1 are potential antigens for mRNA vaccine development against PRAD, and patients in type C1 and C2 are suitable for vaccination.

show abstract

“…There are no predictive markers for cellular danger or proinflammatory responses described for respiratory sensitizers yet. The studies performed up until now did not result in any proteins, genes, or molecular pathways that are consistently regulated by a broad range of respiratory sensitizers or genes 51,52,68 ; however, only a few chemicals have been tested. Cytokine production can be measured by ELISA or Bio-Plex systems either in the supernatants or intracellular matrix.…”

Section: Ke2: Cellular Danger Signals (Activation Of Inflammatory Cytmentioning

confidence: 99%

“…65 The significance of the Nrf2-Keap1 pathway in respiratory sensitization is not as extensively studied compared to skin sensitization, but in vitro data for a limited number of respiratory sensitizers showed that these are able to activate Nrf2-dependent genes both in airway and skin epithelium. [66][67][68] Activation of Nrf2-Keap1 by skin sensitizers has been explained by covalent interaction of cysteine residues on Keap1 with cysteine-reactive chemicals, leading to Nrf2 association and transcriptional activation of genes. It is not fully understood how respiratory sensitizers activate this pathway.…”

Section: Ker: Protein Binding (Mie) Leads To Activation Of Cellular Dmentioning

confidence: 99%

“…72 In a mouse model of TDI-induced asthma, the PTEN pathway was shown to play a protective role in asthma pathogenesis, because it was involved in the regulation of IL-17 induction and NF-jB activation. 73 A more recent in vitro study showed that the PTEN pathway was not consistently induced by all respiratory sensitizers, since maleic anhydride and 7-aminocephalosporanic acid failed to induce this pathway 68 but another diisocyanate, HDI, did.…”

Section: Ker: Protein Binding (Mie) Leads To Activation Of Cellular Dmentioning

confidence: 99%

See 1 more Smart Citation

An Adverse Outcome Pathway for Sensitization of the Respiratory Tract by Low-Molecular-Weight Chemicals: Building Evidence to Support the Utility ofIn VitroandIn SilicoMethods in a Regulatory Context

Sullivan

Enoch

Ezendam

et al. 2017

Applied In Vitro Toxicology

View full text Add to dashboard Cite

Sensitization of the respiratory tract is an important occupational health challenge, and understanding the mechanistic basis of this effect is necessary to support the development of toxicological tools to detect chemicals that may cause it. Here we use the adverse outcome pathway (AOP) framework to organize information that may better inform our understanding of sensitization of the respiratory tract, building on a previously published skin sensitization AOP, relying on literature evidence linked to low-molecular-weight organic chemicals and excluding other known respiratory sensitizers acting via different molecular initiating events. The established key events (KEs) are as follows: (1) covalent binding of chemicals to proteins, (2) activation of cellular danger signals (inflammatory cytokines and chemokines and cytoprotective gene pathways), (3) dendritic cell activation and migration, (4) activation, proliferation, and polarization of T cells, and (5) sensitization of the respiratory tract. These events mirror the skin sensitization AOP but with specific differences. For example, there is some evidence that respiratory sensitizers bind preferentially to lysine moieties, whereas skin sensitizers bind to both cysteine and lysine. Furthermore, exposure to respiratory sensitizers seems to result in cell behavior for KEs 2 and 3, as well as the effector T cell response, in general skewing toward cytokine secretions predominantly associated with T helper 2 (Th2) response. Knowledge gaps include the lack of understanding of which KE(s) drive the Th2 polarization. The construction of this AOP may provide insight into predictive tests that would in combination support the discrimination of respiratory-sensitizing from non-and skin-sensitizing chemicals, a clear regulatory need.

show abstract

Gene expressions changes in bronchial epithelial cells: Markers for respiratory sensitizers and exploration of the NRF2 pathway

Cited by 14 publications

References 36 publications

Analysis of signature genes and association with immune cells infiltration in pediatric septic shock

Analysis of signature genes and association with immune cells infiltration in pediatric septic shock

Identification of Neoantigens and Construction of Immune Subtypes in Prostate Adenocarcinoma

An Adverse Outcome Pathway for Sensitization of the Respiratory Tract by Low-Molecular-Weight Chemicals: Building Evidence to Support the Utility ofIn VitroandIn SilicoMethods in a Regulatory Context

Contact Info

Product

Resources

About