PMID- 25506235
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20141216
LR  - 20200930
IS  - 1178-7031 (Print)
IS  - 1178-7031 (Electronic)
IS  - 1178-7031 (Linking)
VI  - 7
DP  - 2014
TI  - Inhibiting TNF-alpha signaling does not attenuate induction of endotoxin tolerance.
PG  - 159-67
LID - 10.2147/JIR.S75037 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) 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-alpha is responsible 
      for altering vascular permeability and activating infiltrating inflammatory 
      cells, such as monocytes and neutrophils. Interestingly, TNF-alpha has also 
      demonstrated the ability to induce tolerance to subsequent challenges with TNF-alpha 
      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-alpha 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-alpha during the primary response to LPS. To 
      investigate TNF-alpha-dependent tolerance, human monocytic THP-1 cells were treated 
      with TNF-alpha-neutralizing antibodies or antagonistic TNF-alpha receptor antibodies 
      before primary LPS stimulation and then monitored for the production of TNF-alpha 
      during the primary and challenge stimulation. During the primary stimulation, 
      anti-TNF-alpha treatment effectively attenuated the production of TNF-alpha and 
      interleukin-1beta; however, this reduced production did not impact the induction of 
      endotoxin tolerance. These results demonstrate that interfering with TNF-alpha 
      signaling attenuates production of inflammatory cytokines without affecting the 
      induction of tolerance.
FAU - Loosbroock, Christopher
AU  - Loosbroock C
AD  - Department of Microbiology and Immunology, University of Nevada School of 
      Medicine, Reno, NV, USA.
FAU - Hunter, Kenneth W
AU  - Hunter KW
AD  - Department of Microbiology and Immunology, University of Nevada School of 
      Medicine, Reno, NV, USA.
LA  - eng
PT  - Journal Article
DEP - 20141203
PL  - New Zealand
TA  - J Inflamm Res
JT  - Journal of inflammation research
JID - 101512684
PMC - PMC4259568
OTO - NOTNLM
OT  - THP-1 cells
OT  - anti-tumor necrosis factor-alpha
OT  - endotoxin tolerance
OT  - lipopolysaccharide
OT  - tumor necrosis factor-alpha
EDAT- 2014/12/17 06:00
MHDA- 2014/12/17 06:01
PMCR- 2014/12/03
CRDT- 2014/12/16 06:00
PHST- 2014/12/16 06:00 [entrez]
PHST- 2014/12/17 06:00 [pubmed]
PHST- 2014/12/17 06:01 [medline]
PHST- 2014/12/03 00:00 [pmc-release]
AID - jir-7-159 [pii]
AID - 10.2147/JIR.S75037 [doi]
PST - epublish
SO  - J Inflamm Res. 2014 Dec 3;7:159-67. doi: 10.2147/JIR.S75037. eCollection 2014.