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TNF-α Autocrine Feedback Loops in Human Monocytes: The Pro- and Anti-Inflammatory Roles of the TNF-α Receptors Support the Concept of Selective TNFR1 Blockade In Vivo
Joint Authors
Gane, Jennie M.
Stockley, Robert A.
Sapey, Elizabeth
Source
Journal of Immunology Research
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-09-22
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Selective TNFR1 blockade in inflammatory diseases is emerging as a clinical strategy.
We studied the roles of the two TNF-α receptors, TNFR1 and TNFR2, in human monocytes, the principal producer of TNF-α and central to many TNF-α driven diseases.
We hypothesised that TNF-α has pro- and anti-inflammatory effects on monocytes, occurring differentially via TNFR1 and TNFR2.
Monocytes were isolated from healthy human subjects and exposed to LPS, plus/minus the addition of blocking antibodies to TNF-α or its receptors.
Pro- and anti-inflammatory cytokine production was quantified using real-time PCR and ELISAs.
Cell surface expression of TNFR1/2 was measured by flow cytometry.
We demonstrated that monocytes vary in the expression patterns of TNFR1 and TNFR2.
Autocrine binding of TNF-α led to sustained upregulation of proinflammatory cytokines via TNFR1.
In contrast, autocrine binding via TNFR2 upregulated the anti-inflammatory cytokine, IL-10, without proinflammatory effect.
TNFR2 was responsible for binding soluble TNF-α secreted by monocytes, clearing the cytokine from the pericellular environment.
TNFR1 blockade did not change the cell surface expression of TNFR2, leaving this receptor free to upregulate IL-10.
These novel results support the concept of selective TNFR1 blockade in vivo in order that positive anti-inflammatory effects of TNF-α can be retained via TNFR2 ligation.
American Psychological Association (APA)
Gane, Jennie M.& Stockley, Robert A.& Sapey, Elizabeth. 2016. TNF-α Autocrine Feedback Loops in Human Monocytes: The Pro- and Anti-Inflammatory Roles of the TNF-α Receptors Support the Concept of Selective TNFR1 Blockade In Vivo. Journal of Immunology Research،Vol. 2016, no. 2016, pp.1-13.
https://search.emarefa.net/detail/BIM-1108702
Modern Language Association (MLA)
Gane, Jennie M.…[et al.]. TNF-α Autocrine Feedback Loops in Human Monocytes: The Pro- and Anti-Inflammatory Roles of the TNF-α Receptors Support the Concept of Selective TNFR1 Blockade In Vivo. Journal of Immunology Research No. 2016 (2016), pp.1-13.
https://search.emarefa.net/detail/BIM-1108702
American Medical Association (AMA)
Gane, Jennie M.& Stockley, Robert A.& Sapey, Elizabeth. TNF-α Autocrine Feedback Loops in Human Monocytes: The Pro- and Anti-Inflammatory Roles of the TNF-α Receptors Support the Concept of Selective TNFR1 Blockade In Vivo. Journal of Immunology Research. 2016. Vol. 2016, no. 2016, pp.1-13.
https://search.emarefa.net/detail/BIM-1108702
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1108702