Epigallocatechin-3-gallate suppresses proinflammatory cytokines and chemokines induced by Toll-like receptor 9 agonists in prostate cancer cells

Sushovita Mukherjee, Mohammad Adnan Siddiqui, Shubham Dayal, Yasmine Zakaria Ayoub, Krishnamurthy Malathi Department of Biological Sciences, University of Toledo, Toledo, OH, USA Abstract: Chronic inflammation of the prostate contributes to the increased risk of prostate cancer. Microbial pathogen...

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Autores principales:	Mukherjee S, Siddiqui MA, Dayal S, Ayoub YZ, Malathi K
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/b59cf6283b274b2c8082f35f9e6b68da
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spelling	oai:doaj.org-article:b59cf6283b274b2c8082f35f9e6b68da2021-12-02T07:20:16ZEpigallocatechin-3-gallate suppresses proinflammatory cytokines and chemokines induced by Toll-like receptor 9 agonists in prostate cancer cells1178-7031https://doaj.org/article/b59cf6283b274b2c8082f35f9e6b68da2014-06-01T00:00:00Zhttp://www.dovepress.com/epigallocatechin-3-gallate-suppresses-proinflammatory-cytokines-and-ch-a17235https://doaj.org/toc/1178-7031 Sushovita Mukherjee, Mohammad Adnan Siddiqui, Shubham Dayal, Yasmine Zakaria Ayoub, Krishnamurthy Malathi Department of Biological Sciences, University of Toledo, Toledo, OH, USA Abstract: Chronic inflammation of the prostate contributes to the increased risk of prostate cancer. Microbial pathogens in the prostate cause inflammation that leads to prostatitis and proliferative inflammatory atrophy frequently associated with the development of prostate cancer. Bacterial lipopolysaccharides and DNA mediate immune responses by engaging Toll-like receptor (TLR) 4 and 9, respectively. Synthetic oligodeoxynucleotides containing CpG motifs (CpG-ODN) mimic bacterial DNA and signal through TLR9 to initiate innate immune responses. Here, we show that stimulation of DU145, PC3, or LnCap prostate cancer cells by the TLR9 agonists, CpG-ODN, induces mRNA expression of IL-6, IL-8, CXCL1, IP-10, CCL5, and TGFβ. In addition, activity of matrix metalloproteinase (MMP)-9 and -2 and cell migration increased on CpG-ODN treatment. Induction of cytokines and chemokines was mediated by NF-ΚB activation and translocation to the nucleus. Treatment with epigallocatechin-3-gallate (EGCG), the major constituent of green tea, prior to CpG-ODN stimulation, inhibits cytokine and chemokine gene induction, activity of MMP-9 and -2, and cell migration. EGCG treatment sequesters the p65 subunit of transcription factor NF-ΚB in the cytoplasm and inhibits transcriptional activity of the NF-ΚB-driven promoter in response to CpG-ODN. Our results suggest that the ability of the TLR9 agonists, CpG-ODN, to induce cytokines, chemokines, and MMP activity, as well as suppression by EGCG are independent of the androgen receptor and p53 status of the cells. EGCG may provide protective effects against inflammation in the prostate and benefit prostate cancer treatment. Keywords: CpG-ODN, EGCG, inflammation, NF-ΚBMukherjee SSiddiqui MADayal SAyoub YZMalathi KDove Medical PressarticlePathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol 2014, Iss default, Pp 89-101 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Mukherjee S Siddiqui MA Dayal S Ayoub YZ Malathi K Epigallocatechin-3-gallate suppresses proinflammatory cytokines and chemokines induced by Toll-like receptor 9 agonists in prostate cancer cells
description	Sushovita Mukherjee, Mohammad Adnan Siddiqui, Shubham Dayal, Yasmine Zakaria Ayoub, Krishnamurthy Malathi Department of Biological Sciences, University of Toledo, Toledo, OH, USA Abstract: Chronic inflammation of the prostate contributes to the increased risk of prostate cancer. Microbial pathogens in the prostate cause inflammation that leads to prostatitis and proliferative inflammatory atrophy frequently associated with the development of prostate cancer. Bacterial lipopolysaccharides and DNA mediate immune responses by engaging Toll-like receptor (TLR) 4 and 9, respectively. Synthetic oligodeoxynucleotides containing CpG motifs (CpG-ODN) mimic bacterial DNA and signal through TLR9 to initiate innate immune responses. Here, we show that stimulation of DU145, PC3, or LnCap prostate cancer cells by the TLR9 agonists, CpG-ODN, induces mRNA expression of IL-6, IL-8, CXCL1, IP-10, CCL5, and TGFβ. In addition, activity of matrix metalloproteinase (MMP)-9 and -2 and cell migration increased on CpG-ODN treatment. Induction of cytokines and chemokines was mediated by NF-ΚB activation and translocation to the nucleus. Treatment with epigallocatechin-3-gallate (EGCG), the major constituent of green tea, prior to CpG-ODN stimulation, inhibits cytokine and chemokine gene induction, activity of MMP-9 and -2, and cell migration. EGCG treatment sequesters the p65 subunit of transcription factor NF-ΚB in the cytoplasm and inhibits transcriptional activity of the NF-ΚB-driven promoter in response to CpG-ODN. Our results suggest that the ability of the TLR9 agonists, CpG-ODN, to induce cytokines, chemokines, and MMP activity, as well as suppression by EGCG are independent of the androgen receptor and p53 status of the cells. EGCG may provide protective effects against inflammation in the prostate and benefit prostate cancer treatment. Keywords: CpG-ODN, EGCG, inflammation, NF-ΚB
format	article
author	Mukherjee S Siddiqui MA Dayal S Ayoub YZ Malathi K
author_facet	Mukherjee S Siddiqui MA Dayal S Ayoub YZ Malathi K
author_sort	Mukherjee S
title	Epigallocatechin-3-gallate suppresses proinflammatory cytokines and chemokines induced by Toll-like receptor 9 agonists in prostate cancer cells
title_short	Epigallocatechin-3-gallate suppresses proinflammatory cytokines and chemokines induced by Toll-like receptor 9 agonists in prostate cancer cells
title_full	Epigallocatechin-3-gallate suppresses proinflammatory cytokines and chemokines induced by Toll-like receptor 9 agonists in prostate cancer cells
title_fullStr	Epigallocatechin-3-gallate suppresses proinflammatory cytokines and chemokines induced by Toll-like receptor 9 agonists in prostate cancer cells
title_full_unstemmed	Epigallocatechin-3-gallate suppresses proinflammatory cytokines and chemokines induced by Toll-like receptor 9 agonists in prostate cancer cells
title_sort	epigallocatechin-3-gallate suppresses proinflammatory cytokines and chemokines induced by toll-like receptor 9 agonists in prostate cancer cells
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/b59cf6283b274b2c8082f35f9e6b68da
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Epigallocatechin-3-gallate suppresses proinflammatory cytokines and chemokines induced by Toll-like receptor 9 agonists in prostate cancer cells

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