Inhibiting TNF-α signaling does not attenuate induction of endotoxin tolerance

Inhibiting TNF-α signaling does not attenuate induction of endotoxin tolerance

Christopher Loosbroock, Kenneth W Hunter Department of Microbiology and Immunology, University of Nevada School of Medicine, Reno, NV, USA Abstract: Tumor necrosis factor-alpha (TNF-α) is a central mediator of inflammatory responses elicited by Toll-like receptor agonists, such as the Gr...

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Autores principales: Loosbroock C, Hunter KW
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2014
Materias:
Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
Acceso en línea:https://doaj.org/article/05fff9210a3c4b8aaaabd96f8f06e861
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spelling oai:doaj.org-article:05fff9210a3c4b8aaaabd96f8f06e8612021-12-02T00:18:06ZInhibiting TNF-α signaling does not attenuate induction of endotoxin tolerance1178-7031https://doaj.org/article/05fff9210a3c4b8aaaabd96f8f06e8612014-12-01T00:00:00Zhttp://www.dovepress.com/inhibiting-tnf-alpha-signaling-does-not-attenuate-induction-of-endotox-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031 Christopher Loosbroock, Kenneth W Hunter Department of Microbiology and Immunology, University of Nevada School of Medicine, Reno, NV, USA Abstract: Tumor necrosis factor-alpha (TNF-α) is a central mediator of inflammatory responses elicited by Toll-like receptor agonists, such as the Gram-negative bacterial outer membrane antigen lipopolysaccharide (LPS). TNF-α is responsible for altering vascular permeability and activating infiltrating inflammatory cells, such as monocytes and neutrophils. Interestingly, TNF-α has also demonstrated the ability to induce tolerance to subsequent challenges with TNF-α or LPS in monocyte and macrophage cell populations. Tolerance is characterized by the inability to mount a typical inflammatory response during subsequent challenges following the initial exposure to an inflammatory mediator such as LPS. The ability of TNF-α to induce a tolerant-like state with regard to LPS is most likely a regulatory mechanism to prevent excessive inflammation. We hypothesized that the induction of tolerance or the degree of tolerance is dependent upon the production of TNF-α during the primary response to LPS. To investigate TNF-α-dependent tolerance, human monocytic THP-1 cells were treated with TNF-α-neutralizing antibodies or antagonistic TNF-α receptor antibodies before primary LPS stimulation and then monitored for the production of TNF-α during the primary and challenge stimulation. During the primary stimulation, anti-TNF-α treatment effectively attenuated the production of TNF-α and interleukin-1β; however, this reduced production did not impact the induction of endotoxin tolerance. These results demonstrate that interfering with TNF-α signaling attenuates production of inflammatory cytokines without affecting the induction of tolerance. Keywords: endotoxin tolerance, lipopolysaccharide, tumor necrosis factor-alpha, anti-tumor necrosis factor-alpha, THP-1 cellsLoosbroock CHunter KWDove Medical PressarticlePathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol 2014, Iss default, Pp 159-167 (2014)
institution DOAJ
collection DOAJ
language EN
topic Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
spellingShingle Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
Loosbroock C
Hunter KW
Inhibiting TNF-α signaling does not attenuate induction of endotoxin tolerance
description Christopher Loosbroock, Kenneth W Hunter Department of Microbiology and Immunology, University of Nevada School of Medicine, Reno, NV, USA Abstract: Tumor necrosis factor-alpha (TNF-α) is a central mediator of inflammatory responses elicited by Toll-like receptor agonists, such as the Gram-negative bacterial outer membrane antigen lipopolysaccharide (LPS). TNF-α is responsible for altering vascular permeability and activating infiltrating inflammatory cells, such as monocytes and neutrophils. Interestingly, TNF-α has also demonstrated the ability to induce tolerance to subsequent challenges with TNF-α or LPS in monocyte and macrophage cell populations. Tolerance is characterized by the inability to mount a typical inflammatory response during subsequent challenges following the initial exposure to an inflammatory mediator such as LPS. The ability of TNF-α to induce a tolerant-like state with regard to LPS is most likely a regulatory mechanism to prevent excessive inflammation. We hypothesized that the induction of tolerance or the degree of tolerance is dependent upon the production of TNF-α during the primary response to LPS. To investigate TNF-α-dependent tolerance, human monocytic THP-1 cells were treated with TNF-α-neutralizing antibodies or antagonistic TNF-α receptor antibodies before primary LPS stimulation and then monitored for the production of TNF-α during the primary and challenge stimulation. During the primary stimulation, anti-TNF-α treatment effectively attenuated the production of TNF-α and interleukin-1β; however, this reduced production did not impact the induction of endotoxin tolerance. These results demonstrate that interfering with TNF-α signaling attenuates production of inflammatory cytokines without affecting the induction of tolerance. Keywords: endotoxin tolerance, lipopolysaccharide, tumor necrosis factor-alpha, anti-tumor necrosis factor-alpha, THP-1 cells
format article
author Loosbroock C
Hunter KW
author_facet Loosbroock C
Hunter KW
author_sort Loosbroock C
title Inhibiting TNF-α signaling does not attenuate induction of endotoxin tolerance
title_short Inhibiting TNF-α signaling does not attenuate induction of endotoxin tolerance
title_full Inhibiting TNF-α signaling does not attenuate induction of endotoxin tolerance
title_fullStr Inhibiting TNF-α signaling does not attenuate induction of endotoxin tolerance
title_full_unstemmed Inhibiting TNF-α signaling does not attenuate induction of endotoxin tolerance
title_sort inhibiting tnf-α signaling does not attenuate induction of endotoxin tolerance
publisher Dove Medical Press
publishDate 2014
url https://doaj.org/article/05fff9210a3c4b8aaaabd96f8f06e861
work_keys_str_mv AT loosbroockc inhibitingtnfalphasignalingdoesnotattenuateinductionofendotoxintolerance
AT hunterkw inhibitingtnfalphasignalingdoesnotattenuateinductionofendotoxintolerance
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