IL-17A is a central regulator of lung tumor growth

Reppert, Sarah; Koch, Stefan; Finotto, Susetta

doi:10.4161/onci.19735

Cited by 18 publications

(17 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our data showing that IL-17 stimulated IL-6, IL-8 and VEGF expression in the A549 cell line are in accordance with numerous studies reporting that IL-17 augments IL-6203334, IL-8 and VEGF release35 in various types of non-tumour and tumour cells. With regard to lung cancer, IL-17 has been reported to induce IL-6 expression13 in A549 cells, and Numasaki M et al 7. have demonstrated that IL-17 increases IL-6 and IL-8 expression in A549, Sq-19 and LK-87 cells but that VEGF production is not altered in these three cell lines using ELISA.…”

Section: Discussionmentioning

confidence: 99%

“…In lung cancer, IL-17 triggers tumour progression, mainly due to its proangiogenic properties by stimulating the production of angiogenic factors. Many cytokines, such as interleukin-6 (IL-6)13, interleukin-8 (IL-8)1415 and vascular endothelial cell growth factor (VEGF)16, are well-known angiogenic inducers, and IL-17 induces these cytokines in lung cancer. However, the mechanism by which IL-17 mediates the secretion of these angiogenic factors remains unclear.…”

mentioning

confidence: 99%

See 1 more Smart Citation

IL-17 Promotes Angiogenic Factors IL-6, IL-8, and Vegf Production via Stat1 in Lung Adenocarcinoma

Huang

Duan

Qian

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Inflammation and angiogenesis are two hallmarks of carcinoma. The proinflammatory cytokine interleukin-17 (IL-17) facilitates angiogenesis in lung cancer; however, the underlying mechanism is not fully understood. In this study, tumour microvessel density (MVD) was positively associated with IL-17, interleukin-6 (IL-6), interleukin-8 (IL-8), and vascular endothelial cell growth factor (VEGF) expression in human lung adenocarcinoma tissues, and it was increased in tumour tissues of A549-IL-17 cell-bearing nude mice. Importantly, positive correlations were also detected between IL-17 expression and IL-6, IL-8 and VEGF expression in human lung adenocarcinoma tissues. Furthermore, IL-6, IL-8 and VEGF production, as well as STAT1 phosphorylation, were increased in tumour tissues of A549-IL-17 cell-bearing nude mice in vivo and in A549 and H292 cells following IL-17 stimulation in vitro. In addition, STAT1 knockdown using an inhibitor and siRNA attenuated the IL-17-mediated increases in IL-6, IL-8 and VEGF expression in A549 and H292 cells. In conclusion, IL-17 may promote the production of the angiogenic inducers IL-6, IL-8 and VEGF via STAT1 signalling in lung adenocarcinoma.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

IL-17 Promotes Angiogenic Factors IL-6, IL-8, and Vegf Production via Stat1 in Lung Adenocarcinoma

Huang

Duan

Qian

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Th17 cells are a subtype of CD4 + T cells induced by different cytokines, such as IL‐6, TGF‐β1, IL‐23, IL‐21, and IL‐1β . They play an important role in the pathogenesis of several diseases, such as asthma, MS, and cancer . Th17 cells are involved in the induction of EAE, which resembles the early inflammatory phase of MS in humans .…”

Section: Discussionmentioning

confidence: 99%

NFATc1 deficiency in T cells protects mice from experimental autoimmune encephalomyelitis

et al. 2015

Self Cite

View full text Add to dashboard Cite

NFATc1 is a member of the nuclear factor of activated T cells (NFAT) family of transcription factors. NFAT is activated upon T-cell receptor activation followed by intracytoplasmatic Keywords: CD4+ T cells r EAE r NFAT r RORγT r Th17Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionNuclear factor of activated T cells (NFAT) was originally described as a transcription factor inducing the expression of interleukin 2 (IL-2) [1]. The NFAT family of transcription factors consists of five members, named NFAT1-5, and the main forms expressed in T cells are NFATc1 and NFATc2 [2]. NFATc2 is constitutively expressed in T cells [3], whereas NFATc1 is activated upon T-cell receptor stimulation [4]. NFATc1 is the only NFAT protein Correspondence: Prof. Susetta Finotto e-mail: susetta.finotto@uk-erlangen.de family member which acts in a positive autoregulatory loop [5] and thereby augments NFATc1 expression. NFAT proteins reside phosphorylated in the cytoplasm. Upon T-cell receptor activation the phospholipase C signaling pathway is activated, which leads to an induced influx of calcium into the cell. Intracytoplasmatic calcium signaling activates calmodulin, a calcium sensor protein that activates the phosphatase calcineurin. These phosphatase dephosphorylates NFAT proteins, so that they can shuttle into the nucleus where they act as transcription factors on the promoter of target * These authors contributed equally to this work. www.eji-journal.euThis is an open access article under the terms of the Creative Commons Attribution-NonCommercialNoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.Eur. J. Immunol. 2015Immunol. . 45: 1426Immunol. -1440 Immunomodulation 1427 genes such as . Previous studies showed that NFAT proteins play regulatory roles during T-cell differentiation and effector functions. NFATc2 deficiency in T cells diminished Th1 differentiation and induced IL-4 production [7,8]. NFATc2 was also shown to contribute to IL-21 expression and to limit the immunosuppressive function of CD4 + CD25 + Foxp3 + GITR + T regulatory (Treg) cells [8,9]. The role of NFATc1 in T-cell differentiation processes is not fully understood, partially because NFATc1 total knockout mice die at the embryonic stage [10]. Previous analysis on Th1-and Th2-skewed T cells isolated from NFATc1−/− /Rag1 −/− chimeric mice revealed an involvement of NFATc1 in the induction of the Th2-cytokines IL-4 and IL-6, whereas it had no effect on interferon gamma (IFN-γ) and IL-2 expression in Th1 cells [11,12]. Other studies showed that NFATc1 induces IL-4 expression. In Th17 cells, NFAT transcription factors have been shown to be involved in the gene expression of RORγT (where ROR is RARrelated orphan receptor), . This has been shown mostly for other NFAT transcription factor family members than NFATc1. EAE is the murine model for the early in...

show abstract

“…The direct relationship between IL-17A and the increased risk of developing of numerous cancers, including NSCLC, has been demonstrated. On this basis it is considered as the central regulator of lung tumor growth [13]. Among other things, it promotes the migration and invasion of lung cancer cells via the NF-κB/ZEB1 signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the relationship between the IL-17A gene expression level and regulatory miRNA-9 in relation to tumor progression in patients with non-small cell lung cancer: a pilot study

et al. 2019

View full text Add to dashboard Cite

A pro-inflammatory cytokine, IL-17A, is associated with increased risk of developing numerous cancers, including nonsmall cell lung cancer (NSCLC). IL-17A is a target gene for miR-9. This encouraged us to analyze these two genes in terms of their usefulness as prognostic markers in NSCLC. The expression levels of IL-17A gene and miR-9 was assessed in 26 NSCLC tissue samples and 26 unchanged lung tissue adjacent to lung tumors (control tissue), using qPCR. In both tissue groups, a decreased expression of IL-17A was observed in 100% of samples. Increased expression of miRNA-9 was observed in 92% of tumor samples, and in 100% of control samples. Neither statistical differences in the level of expression IL-17A depending on the patient's age, gender, smoking status, nor histopathology of the cancer was found. Regarding the presence of nodule metastasis ('N' value in TNM classification), significantly lower expression level of IL-17A was observed in cN2 as compared with cN1 group. Additionally, statistically lower IL-17A expression was found in III versus II tumor stage (cAJCC classification). Significant negative correlation between both studied genes was revealed in SCC subgroup. This leads to the conclusion that miRNA-9 can regulate the expression of IL-17A as an IL-17A mRNA antagonistic mediator. Inhibition of proinflammatory action of IL-17A in correlation with tumor progression can be related to various activity of Th17 cells on cancer development according to its immunogenicity, and also may suggest suppressive role of IL-17A in tumor progression. However, because of low number of analyzed samples, further studies on the functional role of IL-17A in development and/ or progression NSCLC seem warranted.

show abstract

IL-17A is a central regulator of lung tumor growth

Cited by 18 publications

References 7 publications

IL-17 Promotes Angiogenic Factors IL-6, IL-8, and Vegf Production via Stat1 in Lung Adenocarcinoma

IL-17 Promotes Angiogenic Factors IL-6, IL-8, and Vegf Production via Stat1 in Lung Adenocarcinoma

NFATc1 deficiency in T cells protects mice from experimental autoimmune encephalomyelitis

Evaluation of the relationship between the IL-17A gene expression level and regulatory miRNA-9 in relation to tumor progression in patients with non-small cell lung cancer: a pilot study

Contact Info

Product

Resources

About