Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Lee, Chia-Huei, Hung, Pin-Feng, Lu, Shang-Chieh, Chung, Hsuan-Lien, Chiang, Shang-Lun, Wu, Chun-Te, Chou, Wei-Chun, Sun, Chiao-Yin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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
_version_ 1783482563018358784
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
work_keys_str_mv AT leechiahuei mcp1mcpip1signalingmodulatestheeffectsofil1binrenalcellcarcinomathrougherstressmediatedapoptosis
AT hungpinfeng mcp1mcpip1signalingmodulatestheeffectsofil1binrenalcellcarcinomathrougherstressmediatedapoptosis
AT lushangchieh mcp1mcpip1signalingmodulatestheeffectsofil1binrenalcellcarcinomathrougherstressmediatedapoptosis
AT chunghsuanlien mcp1mcpip1signalingmodulatestheeffectsofil1binrenalcellcarcinomathrougherstressmediatedapoptosis
AT chiangshanglun mcp1mcpip1signalingmodulatestheeffectsofil1binrenalcellcarcinomathrougherstressmediatedapoptosis
AT wuchunte mcp1mcpip1signalingmodulatestheeffectsofil1binrenalcellcarcinomathrougherstressmediatedapoptosis
AT chouweichun mcp1mcpip1signalingmodulatestheeffectsofil1binrenalcellcarcinomathrougherstressmediatedapoptosis
AT sunchiaoyin mcp1mcpip1signalingmodulatestheeffectsofil1binrenalcellcarcinomathrougherstressmediatedapoptosis