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Expression and regulation of toll-like receptors (TLRs) in human intervertebral disc cells
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Expression and regulation of toll-like receptors (TLRs) in human intervertebral disc cells
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Expression and regulation of toll-like receptors (TLRs) in human intervertebral disc cells
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Journal Article
Expression and regulation of toll-like receptors (TLRs) in human intervertebral disc cells
2014
Overview
Purpose
Although inflammatory processes play an essential role in painful intervertebral disc (IVD) degeneration, the underlying regulatory mechanisms are not well understood. This study was designed to investigate the expression, regulation and importance of specific toll-like receptors (TLRs)—which have been shown to play an essential role e.g. in osteoarthritis—during degenerative disc disease.
Methods
The expression of TLRs in human IVDs was measured in isolated cells as well as in normal or degenerated IVD tissue. The role of IL-1β or TNF-α in regulating TLRs (expression/activation) as well as in regulating activity of down-stream pathways (NF-κB) and expression of inflammation-related genes (IL-6, IL-8, HSP60, HSP70, HMGB1) was analyzed.
Results
Expression of TLR1/2/3/4/5/6/9/10 was detected in isolated human IVD cells, with TLR1/2/4/6 being dependent on the degree of IVD degeneration. Stimulation with IL-1β or TNF-α moderately increased TLR1/TLR4 mRNA expression (TNF-α only), and strongly increased TLR2 mRNA expression (IL-1β/TNF-α), with the latter being confirmed on the protein level. Stimulation with IL-1β, TNF-α or Pam3CSK4 (a TLR2-ligand) stimulated IL-6 and IL-8, which was inhibited by a TLR2 neutralizing antibody for Pam3CSK4; IL-1β and TNF-α caused NF-κB activation. HSP60, HSP70 and HMGB1 did not increase IL-6 or IL-8 and were not regulated by IL-1β/TNF-α.
Conclusion
We provide evidence that several TLRs are expressed in human IVD cells, with TLR2 possibly playing the most crucial role. As TLRs mediate catabolic and inflammatory processes, increased levels of TLRs may lead to aggravated disc degeneration, chronic inflammation and pain development. Especially with the identification of more endogenous TLR ligands, targeting these receptors may hold therapeutic promise.
Publisher
Springer Berlin Heidelberg,Springer Nature B.V
Subject
/ Gene Expression Regulation - drug effects
/ Gene Expression Regulation - immunology
/ HSP70 Heat-Shock Proteins - genetics
/ Humans
/ Inflammation Mediators - pharmacology
/ Interleukin-1beta - pharmacology
/ Intervertebral Disc - cytology
/ Intervertebral Disc - immunology
/ Intervertebral Disc - physiology
/ Intervertebral Disc Degeneration - genetics
/ Intervertebral Disc Degeneration - immunology
/ Intervertebral Disc Degeneration - pathology
/ Medicine
/ Mitochondrial Proteins - genetics
/ Osteoarthritis - physiopathology
/ Toll-Like Receptors - genetics
