Genetic variants in IL17A and serum levels of IL-17A are associated with COPD related to tobacco smoking and biomass burning

Ponce-Gallegos, Marco Antonio; Pérez-Rubio, Gloría; Ambrocio-Ortiz, Enrique; Partida-Zavala, Neftali; Hernández-Zenteno, Rafael de Jesús; Flores-Trujillo, Fernando; García-Gómez, Leonor; Hernández-Pérez, Andrea; Ramírez‐Venegas, Alejandra; Falfán-Valencia, Ramcés

doi:10.1038/s41598-020-57606-6

Cited by 16 publications

(13 citation statements)

References 53 publications

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“…In COPD related to cigarette smoke exposure, higher frequency of CD4+ Th17 cells and level of IL-17A in peripheral blood was described comparing with COPD with biomass-burning exposure. 53,54 However, we found no distinct difference of distribution of smokers and non-smokers among three clusters in our study (as shown in Table 2), no difference of cytokine levels between patients with and without smoking history, either (as shown in Table S3). Moreover, some researchers showed the altered IL-17A production related to functional single nucleotide polymorphism (SNP) in promotor of IL-17A gene.…”

Section: Discussioncontrasting

confidence: 55%

<p>Th1/Th17 Cytokine Profiles are Associated with Disease Severity and Exacerbation Frequency in COPD Patients</p>

Zhao

Xie

et al. 2020

COPD

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Background: T helper (Th) cell cytokine imbalances have been associated with the pathophysiology of chronic obstructive pulmonary disease (COPD), including the Th1/Th2 and Th17/T regulatory cells (Treg) paradigms. Clarifying cytokine profiles during COPD acute exacerbation (AE) and their relationships with clinical manifestations would help in understanding the pathogenesis of disease and improve clinical management. Materials and Methods: Eighty seven patients admitted to the hospital with AEs of COPD were included in this study, and follow-up was conducted after discharge (every 30 days, for a total of 120 days). Sputum samples of patients at different time points (including at admission, discharge, and follow-up) were collected, and sputum cytokine profiling (12 cytokines in total) was performed using a Luminex assay. Results: According to the cytokine profiles at admission, patients were divided into three clusters by a k-means clustering algorithm, namely, Th1 high Th17 high (n=26), Th1 low Th17 low (n=56), and Th1 high Th17 low (n=5), which revealed distinct clinical characteristics. Patients with Th1 high Th17 low profile had a significantly longer length of non-invasive ventilation time and length of hospital stay than patients with Th1 high Th17 high profile (7 vs 0 days, 22 vs 11 days, respectively, p < 0.05), and had the highest AE frequency. Sputum levels of Th17 cytokines (IL-17A, IL-22, and IL-23) during AE were negatively correlated with AE frequency in the last 12 months (r = −0.258, −0.289 and −0.216, respectively, p < 0.05). Moreover, decreased sputum IL-17A levels were independently associated with increased AE frequency, with an OR (95% CI) of 0.975 (0.958-0.993) and p = 0.006. Conclusion: Th1/Th17 imbalance during AE is associated with the severity of COPD. Decreased Th17 cytokine expression is correlated with increased AE frequency. The Th1/ Th17 balance may be a specific target for the therapeutic manipulation of COPD.

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Section: Discussioncontrasting

confidence: 55%

<p>Th1/Th17 Cytokine Profiles are Associated with Disease Severity and Exacerbation Frequency in COPD Patients</p>

Zhao

Xie

et al. 2020

COPD

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“…Ponce-Garrez et al showed an association between a polymorphism in the cytokine IL-17A and lung disease development. Additionally, this group found increased IL-17 serum levels in all smokers, independent of COPD development 32 . These results support our previous findings that showed significantly increased IL-17+ cell density in the small airways of smokers with or without COPD.…”

Section: Discussionmentioning

confidence: 74%

“…The Th17 response has been extensively described as playing a pivotal role in autoimmune diseases 31 and more recently in COPD development and progression 32 . Ponce-Garrez et al showed an association between a polymorphism in the cytokine IL-17A and lung disease development.…”

Section: Discussionmentioning

confidence: 99%

Th17/Treg imbalance in COPD development: suppressors of cytokine signaling and signal transducers and activators of transcription proteins

Silva

Lourenço

Silva

et al. 2020

Sci Rep

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Th17/Treg imbalance contributes to chronic obstructive pulmonary disease (COPD) development and progression. However, intracellular signaling by suppressor of cytokine signaling (SOCS) 1 and SOCS3 and the proteins signal transducer and activator of transcription (STAT) 3 and STAT5 that orchestrate these imbalances are currently poorly understood. Thus, these proteins were investigated in C57BL/6 mice after exposure to cigarette smoke (CS) for 3 and 6 months. The expression of interleukin was measured by ELISA and the density of positive cells in peribronchovascular areas was quantified by immunohistochemistry. We showed that exposure to CS in the 3rd month first induced decreases in the numbers of STAT5+ and pSTAT5+ cells and the expression levels of TGF-β and IL-10. The increases in the numbers of STAT3+ and pSTAT3+ cells and IL-17 expression occurred later (6th month). These findings corroborate the increases in the number of SOCS1+ cells in both the 3rd and 6th months, with concomitant decreases in SOCS3+ cells at the same time points. Our results demonstrated that beginning with the initiation of COPD development, there was a downregulation of the anti-inflammatory response mediated by SOCS and STAT proteins. These results highlight the importance of intracellular signaling in Th17/Treg imbalance and the identification of possible targets for future therapeutic approaches.

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“…Four SNPs across IL-17A, viz., rs8193036(C > T), rs8193037(G > A), rs2275913(G > A), and rs3748067(C > T) loci, located in the promoter region or 3′ UTR were examined in this study due to their considerable associations with various malignancies, including NSCLC, and chronic inflammatory respiratory diseases, such as chronic obstructive pulmonary disease, in previous studies [ 18 , 19 , 20 , 26 , 27 ]. Peripheral blood samples from LUAD patients were collected in EDTA-containing tubes for genomic DNA extraction using the QIAamp DNA Blood Mini kit (Qiagen).…”

Section: Methodsmentioning

confidence: 99%

Potential Impacts of Interleukin-17A Promoter Polymorphisms on the EGFR Mutation Status and Progression of Non-Small Cell Lung Cancer in Taiwan

Lee

Lai

Wang

et al. 2021

Genes

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Non-small cell lung cancer (NSCLC) is a typical inflammation-associated cancer, and lung adenocarcinoma (LUAD) is the most common histopathological subtype. Epidermal growth factor receptor (EGFR) mutations are the most common driver mutations of LUAD, and they have been identified as important therapeutic targets by EGFR tyrosine kinase inhibitors. Interleukin (IL)-17A secreted by T-helper 17 lymphocytes is a proinflammatory cytokine that plays an important role in cancer pathogenesis. The present study was designed to investigate the possible associations among IL-17A genetic polymorphisms, EGFR mutation status, and the clinicopathologic development of LUAD in a Taiwanese population. Our study population consisted of 277 LUAD patients harboring the wild-type (WT) EGFR or a mutant (MT) EGFR. Four single-nucleotide polymorphisms (SNPs) of IL-17A in the peripheral blood, including rs8193036(C > T), rs8193037(G > A), rs2275913(G > A), and rs3748067(C > T) loci, were genotyped using a TaqMan allelic discrimination assay. Our results showed that none of these IL-17A SNPs were correlated with the risk of developing mutant EGFR. However, patients with a smoking habit who carried the GA genotype of IL-17A rs8193037 had a significantly lower susceptibility to EGFR mutations (adjusted odds ratio (AOR): 0.225; 95% confidence interval (CI): 0.056~0.900, p = 0.035). Moreover, compared to individuals carrying the CC genotype of rs8193036 at IL-17A, T-allele carriers (CT + TT) were at higher risk of developing more-advanced stages (stage III or IV; p = 0.020). In the WT EGFR subgroup analysis, IL-17A rs8193036 T-allele carriers had higher risks of developing an advanced tumor stage (p = 0.016) and lymphatic invasion (p = 0.049). Further analyses of clinical datasets revealed correlations of IL-17 receptor A (IL-17RA) and IL-17RC expressions with a poor prognosis of LUAD patients with a smoking history or with higher levels of tumor-infiltrating lymphocytes. In conclusion, our results suggested that two functional promoter polymorphisms of IL-17A, i.e., rs8193036 and rs8193037, were associated with the EGFR mutation status and progression in LUAD patients, indicating that these two genetic variants might act as possible markers for predicting patients’ clinical prognoses.

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Genetic variants in IL17A and serum levels of IL-17A are associated with COPD related to tobacco smoking and biomass burning

Cited by 16 publications

References 53 publications

<p>Th1/Th17 Cytokine Profiles are Associated with Disease Severity and Exacerbation Frequency in COPD Patients</p>

<p>Th1/Th17 Cytokine Profiles are Associated with Disease Severity and Exacerbation Frequency in COPD Patients</p>

Th17/Treg imbalance in COPD development: suppressors of cytokine signaling and signal transducers and activators of transcription proteins

Potential Impacts of Interleukin-17A Promoter Polymorphisms on the EGFR Mutation Status and Progression of Non-Small Cell Lung Cancer in Taiwan

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