Interleukin 17 Induces Up-Regulation of Chemokine and Cytokine Expression Via Activation of the Nuclear Factor κB and Extracellular Signal–Regulated Kinase 1/2 Pathways in Gynecologic Cancer Cell Lines

Lai, Ting; Wang, Kana; Hou, Qiannan; Zhang, Jian; Yuan, Jianyong; Yuan, Lixing; You, Zongbing; Xi, Mingrong

doi:10.1097/igc.0b013e31822d2abd

Cited by 19 publications

(14 citation statements)

References 19 publications

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“…In Myc-CaP/CR cells, neither U0126 nor PDTC inhibited IL-17A-induced COX-2 protein expression (data not shown). These findings suggest that IL-17 indeed acts through NF-κB and ERK1/2 signaling pathways in A549 and HeLa cells to regulate expression of downstream genes, which is consistent with our previous study [11]. …”

Section: Resultssupporting

confidence: 93%

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Interleukin-17 Indirectly Promotes M2 Macrophage Differentiation through Stimulation of COX-2/PGE2 Pathway in the Cancer Cells

Liu

Zhang

et al. 2014

Cancer Res Treat

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PurposeInterleukin-17 (IL-17) is a proinflammatory cytokine that plays important roles in inflammation, autoimmunity, and cancer. The purpose of this study was to determine if IL-17 indirectly regulates macrophage differentiation through up-regulation of cyclooxygenase-2 (COX-2) expression in the cancer cell lines.Materials and MethodsHuman cervical cancer HeLa, human lung cancer A549, and mouse prostate cancer Myc-CaP/CR cell lines were treated with recombinant IL-17; Western blot analysis, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction analysis were utilized to examine the cellular responses.ResultsIL-17 up-regulated expression of COX-2 mRNA and protein in HeLa, A549, and Myc- CaP/CR cell lines. IL-17’s effects were mediated through nuclear factor-κB and ERK1/2 signaling pathways as the inhibitors of these pathways could inhibit IL-17- induced COX-2 expression. The conditional medium obtained from the cancer cells contained prostaglandin E2, the levels of which were increased by IL-17 treatment. When treated with the conditional medium, particularly with the IL-17-induced conditional medium, mouse RAW264.7 macrophages and human THP-1 monocytes expressed higher levels of IL-10 (a marker of M2 macrophages) than inducible nitric oxide synthase or tumor necrosis factor α (markers of M1 macrophages). In contrast, when RAW264.7 and THP-1 cells were treated directly with IL-17, expression of these marker genes was not markedly changed.ConclusionThe results of this study suggest that IL-17 indirectly promotes M2 macrophage differentiation through stimulation of the COX-2/PGE2 pathway in the cancer cells, thus IL-17 plays an indirect role in regulating the tumor immune microenvironment.

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Section: Resultssupporting

confidence: 93%

“…We have previously shown that IL-17 up-regulates expression of chemokines and cytokines in human cancer cell lines such as HeLa, HEC-1-B, and SKOV3 [11]. In this study, we found that IL-17 significantly up-regulated COX-2 mRNA expression in HeLa, A549, and Myc-CaP/CR cancer cell lines (p < 0.05) (Fig.…”

Section: Resultssupporting

confidence: 54%

Interleukin-17 Indirectly Promotes M2 Macrophage Differentiation through Stimulation of COX-2/PGE2 Pathway in the Cancer Cells

Liu

Zhang

et al. 2014

Cancer Res Treat

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“…Previous studies did not find an effect of IL-17 on HeLa and IC1 cervical cancer cell growth. 33,34 These results suggest that IL-17 may increase cellular tightness in cervical cancer cells. Additionally, both a high number of IL-17…”

Section: Discussionmentioning

confidence: 75%

Angels and demons: Th17 cells represent a beneficial response, while neutrophil IL-17 is associated with poor prognosis in squamous cervical cancer

Punt¹,

Fleuren²,

Kritikou³

et al. 2015

OncoImmunology

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“…As shown in Figure 5A, miR-23b expression was decreased in IL-17A-treated cells at 3 and 6 h and returned to baseline at 24 h. NF-κB was a crucial target of IL-17A signaling pathway in many types of cells [31–33] and it had been reported to function as a tumor promoter in inflammation-associated cancer [34]. Western blot analysis showed that IL-17A increased the protein level of p65 in the nuclear fraction and decreased it in the cytosolic fraction (Figure 5B).…”

Section: Resultsmentioning

confidence: 99%

Interleukin-17A promotes tongue squamous cell carcinoma metastasis through activating miR-23b/versican pathway

et al. 2016

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Interleukin-17A (IL-17A), a proinflammatory cytokine mainly produced by T helper 17 cells, exerts protumor or antitumor effects in different cancer entities. However, the exact role of IL-17A in carcinogenesis and progression of tongue squamous cell carcinoma (TSCC) remains unclear. Here, we found that the levels of IL-17A in serum and tumor samples were significantly increased in TSCC patients and positively correlated with tumor metastasis and clinical stage. Besides, IL-17A enhanced cell migration and invasion in SCC15, a TSCC cell line. Furthermore, IL-17A inversely correlated with miR-23b expression in TSCC specimens. In vitro, NF-κB inhibited miR-23b transcription by directly binding to its promoter region. IL-17A downregulated miR-23b expression via activating NF-κB signaling pathway characterized by increasing p65 expression in the nuclear and elevating the levels of p-IKKα and p-IκBα. Overexpression of miR-23b inhibited, whereas knockdown of miR-23b promoted migration and invasion abilities of SCC15 cells. Moreover, extracellular matrix protein versican was proved to be the direct target of miR-23b through luciferase assay. IL-17A increased versican levels in vitro and knockdown of versican by siRNA inhibited SCC15 cell migration and invasion. Taken together, these results reveal a novel mechanism that IL-17A in TSCC microenvironment promotes the migration and invasion of TSCC cells through targeting miR-23b/versican pathway.

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Interleukin 17 Induces Up-Regulation of Chemokine and Cytokine Expression Via Activation of the Nuclear Factor κB and Extracellular Signal–Regulated Kinase 1/2 Pathways in Gynecologic Cancer Cell Lines

Abstract: These results demonstrated that IL-17 may regulate chemokines and cytokines in gynecologic cancers.

Cited by 19 publications

References 19 publications

Interleukin-17 Indirectly Promotes M2 Macrophage Differentiation through Stimulation of COX-2/PGE2 Pathway in the Cancer Cells

Interleukin-17 Indirectly Promotes M2 Macrophage Differentiation through Stimulation of COX-2/PGE2 Pathway in the Cancer Cells

Angels and demons: Th17 cells represent a beneficial response, while neutrophil IL-17 is associated with poor prognosis in squamous cervical cancer

Interleukin-17A promotes tongue squamous cell carcinoma metastasis through activating miR-23b/versican pathway

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