Increased Death of Peripheral Blood Mononuclear Cells after TLR4 Inhibition in Sepsis Is Not via TNF/TNF Receptor-Mediated Apoptotic Pathway

Background. Apoptosis is one of the causes of immune depression in sepsis. Pyroptosis also occurs in sepsis. The toll-like receptor (TLR) 4 and receptor for advanced glycation end products (RAGE) have been shown to play important roles in apoptosis and pyroptosis. However, it is still unknown whethe...

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Autores principales:	Chien-Ming Chu, Li-Chung Chiu, Chung-Chieh Yu, Li-Pang Chuang, Kuo-Chin Kao, Li-Fu Li, Huang-Pin Wu
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Pathology RB1-214
Acceso en línea:	https://doaj.org/article/899fff3f6bae431f9f4424123d612356
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spelling	oai:doaj.org-article:899fff3f6bae431f9f4424123d6123562021-11-08T02:36:45ZIncreased Death of Peripheral Blood Mononuclear Cells after TLR4 Inhibition in Sepsis Is Not via TNF/TNF Receptor-Mediated Apoptotic Pathway1466-186110.1155/2021/2255017https://doaj.org/article/899fff3f6bae431f9f4424123d6123562021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/2255017https://doaj.org/toc/1466-1861Background. Apoptosis is one of the causes of immune depression in sepsis. Pyroptosis also occurs in sepsis. The toll-like receptor (TLR) 4 and receptor for advanced glycation end products (RAGE) have been shown to play important roles in apoptosis and pyroptosis. However, it is still unknown whether TLR4 inhibition decreases apoptosis in sepsis. Methods. Stimulated peripheral blood mononuclear cells (PBMCs) with or without lipopolysaccharides (LPS) and high-mobility group box 1 (HMGB1) were cultured with or without TLR4 inhibition using monoclonal antibodies from 20 patients with sepsis. Caspase-3, caspase-8, and caspase-9 activities were measured. The expression of B cell lymphoma 2 (Bcl2) and Bcl2-associated X (Bax) was measured. The cell death of PBMCs was detected using a flow cytofluorimeter. Results. After TLR4 inhibition, Bcl2 to Bax ratio elevated both in LPS and HMGB1-stimulated PBMCs. The activities of caspase-3, caspase-8, and caspase-9 did not change in LPS or HMGB1-stimulated PBMCs. The cell death of LPS and HMGB1-stimulated CD8 lymphocytes and monocytes increased after TLR4 inhibition. The cell death of CD4 lymphocytes was unchanged. Conclusion. The apoptosis did not decrease, while TLR4 was inhibited. After TLR4 inhibition, there was an unknown mechanism to keep cell death in stimulated PBMCs in patients with sepsis.Chien-Ming ChuLi-Chung ChiuChung-Chieh YuLi-Pang ChuangKuo-Chin KaoLi-Fu LiHuang-Pin WuHindawi LimitedarticlePathologyRB1-214ENMediators of Inflammation, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pathology RB1-214
spellingShingle	Pathology RB1-214 Chien-Ming Chu Li-Chung Chiu Chung-Chieh Yu Li-Pang Chuang Kuo-Chin Kao Li-Fu Li Huang-Pin Wu Increased Death of Peripheral Blood Mononuclear Cells after TLR4 Inhibition in Sepsis Is Not via TNF/TNF Receptor-Mediated Apoptotic Pathway
description	Background. Apoptosis is one of the causes of immune depression in sepsis. Pyroptosis also occurs in sepsis. The toll-like receptor (TLR) 4 and receptor for advanced glycation end products (RAGE) have been shown to play important roles in apoptosis and pyroptosis. However, it is still unknown whether TLR4 inhibition decreases apoptosis in sepsis. Methods. Stimulated peripheral blood mononuclear cells (PBMCs) with or without lipopolysaccharides (LPS) and high-mobility group box 1 (HMGB1) were cultured with or without TLR4 inhibition using monoclonal antibodies from 20 patients with sepsis. Caspase-3, caspase-8, and caspase-9 activities were measured. The expression of B cell lymphoma 2 (Bcl2) and Bcl2-associated X (Bax) was measured. The cell death of PBMCs was detected using a flow cytofluorimeter. Results. After TLR4 inhibition, Bcl2 to Bax ratio elevated both in LPS and HMGB1-stimulated PBMCs. The activities of caspase-3, caspase-8, and caspase-9 did not change in LPS or HMGB1-stimulated PBMCs. The cell death of LPS and HMGB1-stimulated CD8 lymphocytes and monocytes increased after TLR4 inhibition. The cell death of CD4 lymphocytes was unchanged. Conclusion. The apoptosis did not decrease, while TLR4 was inhibited. After TLR4 inhibition, there was an unknown mechanism to keep cell death in stimulated PBMCs in patients with sepsis.
format	article
author	Chien-Ming Chu Li-Chung Chiu Chung-Chieh Yu Li-Pang Chuang Kuo-Chin Kao Li-Fu Li Huang-Pin Wu
author_facet	Chien-Ming Chu Li-Chung Chiu Chung-Chieh Yu Li-Pang Chuang Kuo-Chin Kao Li-Fu Li Huang-Pin Wu
author_sort	Chien-Ming Chu
title	Increased Death of Peripheral Blood Mononuclear Cells after TLR4 Inhibition in Sepsis Is Not via TNF/TNF Receptor-Mediated Apoptotic Pathway
title_short	Increased Death of Peripheral Blood Mononuclear Cells after TLR4 Inhibition in Sepsis Is Not via TNF/TNF Receptor-Mediated Apoptotic Pathway
title_full	Increased Death of Peripheral Blood Mononuclear Cells after TLR4 Inhibition in Sepsis Is Not via TNF/TNF Receptor-Mediated Apoptotic Pathway
title_fullStr	Increased Death of Peripheral Blood Mononuclear Cells after TLR4 Inhibition in Sepsis Is Not via TNF/TNF Receptor-Mediated Apoptotic Pathway
title_full_unstemmed	Increased Death of Peripheral Blood Mononuclear Cells after TLR4 Inhibition in Sepsis Is Not via TNF/TNF Receptor-Mediated Apoptotic Pathway
title_sort	increased death of peripheral blood mononuclear cells after tlr4 inhibition in sepsis is not via tnf/tnf receptor-mediated apoptotic pathway
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/899fff3f6bae431f9f4424123d612356
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Increased Death of Peripheral Blood Mononuclear Cells after TLR4 Inhibition in Sepsis Is Not via TNF/TNF Receptor-Mediated Apoptotic Pathway

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