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MCP-1/MCPIP-1 Signaling Modulates the Effects of IL-1β in Renal Cell Carcinoma through ER Stress-Mediated Apoptosis
In renal cell carcinoma (RCC), interleukin (IL)-1β may be a pro-metastatic cytokine. However, we have not yet noted the clinical association between tumoral expression or serum level of IL-1β and RCC in our patient cohort. Herein, we investigate molecular mechanisms elicited by IL-1β in RCC. We foun...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928829/ https://www.ncbi.nlm.nih.gov/pubmed/31816951 http://dx.doi.org/10.3390/ijms20236101 |
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author | Lee, Chia-Huei Hung, Pin-Feng Lu, Shang-Chieh Chung, Hsuan-Lien Chiang, Shang-Lun Wu, Chun-Te Chou, Wei-Chun Sun, Chiao-Yin |
author_facet | Lee, Chia-Huei Hung, Pin-Feng Lu, Shang-Chieh Chung, Hsuan-Lien Chiang, Shang-Lun Wu, Chun-Te Chou, Wei-Chun Sun, Chiao-Yin |
author_sort | Lee, Chia-Huei |
collection | PubMed |
description | In renal cell carcinoma (RCC), interleukin (IL)-1β may be a pro-metastatic cytokine. However, we have not yet noted the clinical association between tumoral expression or serum level of IL-1β and RCC in our patient cohort. Herein, we investigate molecular mechanisms elicited by IL-1β in RCC. We found that IL-1β stimulates substantial monocyte chemoattractant protein (MCP)-1 production in RCC cells by activating NF-kB and AP-1. In our xenograft RCC model, intra-tumoral MCP-1 injection down-regulated Ki67 expression and reduced tumor size. Microarray analysis revealed that MCP-1 treatment altered protein-folding processes in RCC cells. MCP-1-treated RCC cells and xenograft tumors expressed MCP-1-induced protein (MCPIP) and molecules involved in endoplasmic reticulum (ER) stress-mediated apoptosis, namely C/EBP Homologous Protein (CHOP), protein kinase-like ER kinase (PERK), and calnexin (CNX). ER stress-mediated apoptosis in MCP-1-treated RCC cells was confirmed using Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) assay. Moreover, ectopic MCPIP expression increased PERK expression in Human embryonic kidney (HEK)293 cells. Our meta-analysis revealed that low MCP-1 levels reduce 1-year post-nephrectomy survival in patients with RCC. Immunohistochemistry indicated that in some RCC biopsy samples, the correlation between MCP-1 or MCPIP expression and tumor stages was inverse. Thus, MCP-1 and MCPIP potentially reduce the IL-1β-mediated oncogenic effect in RCC; our findings suggest that ER stress is a potential RCC treatment target. |
format | Online Article Text |
id | pubmed-6928829 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-69288292019-12-26 MCP-1/MCPIP-1 Signaling Modulates the Effects of IL-1β in Renal Cell Carcinoma through ER Stress-Mediated Apoptosis Lee, Chia-Huei Hung, Pin-Feng Lu, Shang-Chieh Chung, Hsuan-Lien Chiang, Shang-Lun Wu, Chun-Te Chou, Wei-Chun Sun, Chiao-Yin Int J Mol Sci Article In renal cell carcinoma (RCC), interleukin (IL)-1β may be a pro-metastatic cytokine. However, we have not yet noted the clinical association between tumoral expression or serum level of IL-1β and RCC in our patient cohort. Herein, we investigate molecular mechanisms elicited by IL-1β in RCC. We found that IL-1β stimulates substantial monocyte chemoattractant protein (MCP)-1 production in RCC cells by activating NF-kB and AP-1. In our xenograft RCC model, intra-tumoral MCP-1 injection down-regulated Ki67 expression and reduced tumor size. Microarray analysis revealed that MCP-1 treatment altered protein-folding processes in RCC cells. MCP-1-treated RCC cells and xenograft tumors expressed MCP-1-induced protein (MCPIP) and molecules involved in endoplasmic reticulum (ER) stress-mediated apoptosis, namely C/EBP Homologous Protein (CHOP), protein kinase-like ER kinase (PERK), and calnexin (CNX). ER stress-mediated apoptosis in MCP-1-treated RCC cells was confirmed using Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) assay. Moreover, ectopic MCPIP expression increased PERK expression in Human embryonic kidney (HEK)293 cells. Our meta-analysis revealed that low MCP-1 levels reduce 1-year post-nephrectomy survival in patients with RCC. Immunohistochemistry indicated that in some RCC biopsy samples, the correlation between MCP-1 or MCPIP expression and tumor stages was inverse. Thus, MCP-1 and MCPIP potentially reduce the IL-1β-mediated oncogenic effect in RCC; our findings suggest that ER stress is a potential RCC treatment target. MDPI 2019-12-03 /pmc/articles/PMC6928829/ /pubmed/31816951 http://dx.doi.org/10.3390/ijms20236101 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lee, Chia-Huei Hung, Pin-Feng Lu, Shang-Chieh Chung, Hsuan-Lien Chiang, Shang-Lun Wu, Chun-Te Chou, Wei-Chun Sun, Chiao-Yin MCP-1/MCPIP-1 Signaling Modulates the Effects of IL-1β in Renal Cell Carcinoma through ER Stress-Mediated Apoptosis |
title | MCP-1/MCPIP-1 Signaling Modulates the Effects of IL-1β in Renal Cell Carcinoma through ER Stress-Mediated Apoptosis |
title_full | MCP-1/MCPIP-1 Signaling Modulates the Effects of IL-1β in Renal Cell Carcinoma through ER Stress-Mediated Apoptosis |
title_fullStr | MCP-1/MCPIP-1 Signaling Modulates the Effects of IL-1β in Renal Cell Carcinoma through ER Stress-Mediated Apoptosis |
title_full_unstemmed | MCP-1/MCPIP-1 Signaling Modulates the Effects of IL-1β in Renal Cell Carcinoma through ER Stress-Mediated Apoptosis |
title_short | MCP-1/MCPIP-1 Signaling Modulates the Effects of IL-1β in Renal Cell Carcinoma through ER Stress-Mediated Apoptosis |
title_sort | mcp-1/mcpip-1 signaling modulates the effects of il-1β in renal cell carcinoma through er stress-mediated apoptosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928829/ https://www.ncbi.nlm.nih.gov/pubmed/31816951 http://dx.doi.org/10.3390/ijms20236101 |
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