Tags

Type your tag names separated by a space and hit enter

Toll-Like Receptor 4 (TLR4) expression and stimulation in a model of intervertebral disc inflammation and degeneration.
Spine (Phila Pa 1976). 2013 Jul 15; 38(16):1343-51.S

Abstract

STUDY DESIGN

We measured the expression and responses of Toll-Like Receptor 4 (TLR4) activation in the intervertebral disc (IVD) in vitro and in vivo. We hypothesize that stimulation of the IVD with the TLR4 ligand lipopolysaccharide (LPS) results in upregulation of a coordinated set of proinflammatory mediators and inhibition of matrix expression, both consistent with a molecular profile of degeneration.

OBJECTIVE

To characterize early inflammatory and morphological changes induced by TLR4 activation in the IVD.

SUMMARY OF BACKGROUND DATA

TLR4 is a pattern recognition receptor activated in innate immunity that has been implicated in disease mechanisms of inflammatory cartilaginous degeneration. However, no study to date has examined the expression and responses of TLR4 in the IVD.

METHODS

IVD cells were stimulated with LPS in a dose-dependent manner, and inflammatory cytokine levels were measured by quantitative reverse transcription-polymerase chain reaction. Histological and inflammatory changes due to in vivo injection of LPS into the rat caudal IVD were measured by enzyme-linked immunosorbent assay and immunoblotting.

RESULTS

Baseline TLR4 expression in IVD tissue varied according to cell type. LPS stimulation resulted in significant increases in tumor necrosis factor α (TNF)-α, interleukin (IL)-1β, IL-6, and nitric oxide levels and significant inhibition in aggrecan and collagen-2. Intradiscal injection of LPS was found to cause moderate degenerative changes in the IVD, with increases in tissue levels of IL-1β, TNF-α, high mobility group box 1 protein (HMGB1), and macrophage migration inhibitory factor (MIF).

CONCLUSION

This study provides the first evidence that IVD cells express TLR4 and are responsive to TLR4 activation by upregulating a coordinated set of inflammatory cytokines. This study suggests that intradiscal injection of LPS offers a model for triggering inflammation of the IVD, demonstrating that inflammatory insults alone may potentially trigger degenerative changes of the IVD.

Authors+Show Affiliations

The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22850250

Citation

Rajan, Neena E., et al. "Toll-Like Receptor 4 (TLR4) Expression and Stimulation in a Model of Intervertebral Disc Inflammation and Degeneration." Spine, vol. 38, no. 16, 2013, pp. 1343-51.
Rajan NE, Bloom O, Maidhof R, et al. Toll-Like Receptor 4 (TLR4) expression and stimulation in a model of intervertebral disc inflammation and degeneration. Spine. 2013;38(16):1343-51.
Rajan, N. E., Bloom, O., Maidhof, R., Stetson, N., Sherry, B., Levine, M., & Chahine, N. O. (2013). Toll-Like Receptor 4 (TLR4) expression and stimulation in a model of intervertebral disc inflammation and degeneration. Spine, 38(16), 1343-51. https://doi.org/10.1097/BRS.0b013e31826b71f4
Rajan NE, et al. Toll-Like Receptor 4 (TLR4) Expression and Stimulation in a Model of Intervertebral Disc Inflammation and Degeneration. Spine. 2013 Jul 15;38(16):1343-51. PubMed PMID: 22850250.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Toll-Like Receptor 4 (TLR4) expression and stimulation in a model of intervertebral disc inflammation and degeneration. AU - Rajan,Neena E, AU - Bloom,Ona, AU - Maidhof,Robert, AU - Stetson,Nathanial, AU - Sherry,Barbara, AU - Levine,Mitchell, AU - Chahine,Nadeen O, PY - 2012/8/2/entrez PY - 2012/8/2/pubmed PY - 2014/2/11/medline SP - 1343 EP - 51 JF - Spine JO - Spine VL - 38 IS - 16 N2 - STUDY DESIGN: We measured the expression and responses of Toll-Like Receptor 4 (TLR4) activation in the intervertebral disc (IVD) in vitro and in vivo. We hypothesize that stimulation of the IVD with the TLR4 ligand lipopolysaccharide (LPS) results in upregulation of a coordinated set of proinflammatory mediators and inhibition of matrix expression, both consistent with a molecular profile of degeneration. OBJECTIVE: To characterize early inflammatory and morphological changes induced by TLR4 activation in the IVD. SUMMARY OF BACKGROUND DATA: TLR4 is a pattern recognition receptor activated in innate immunity that has been implicated in disease mechanisms of inflammatory cartilaginous degeneration. However, no study to date has examined the expression and responses of TLR4 in the IVD. METHODS: IVD cells were stimulated with LPS in a dose-dependent manner, and inflammatory cytokine levels were measured by quantitative reverse transcription-polymerase chain reaction. Histological and inflammatory changes due to in vivo injection of LPS into the rat caudal IVD were measured by enzyme-linked immunosorbent assay and immunoblotting. RESULTS: Baseline TLR4 expression in IVD tissue varied according to cell type. LPS stimulation resulted in significant increases in tumor necrosis factor α (TNF)-α, interleukin (IL)-1β, IL-6, and nitric oxide levels and significant inhibition in aggrecan and collagen-2. Intradiscal injection of LPS was found to cause moderate degenerative changes in the IVD, with increases in tissue levels of IL-1β, TNF-α, high mobility group box 1 protein (HMGB1), and macrophage migration inhibitory factor (MIF). CONCLUSION: This study provides the first evidence that IVD cells express TLR4 and are responsive to TLR4 activation by upregulating a coordinated set of inflammatory cytokines. This study suggests that intradiscal injection of LPS offers a model for triggering inflammation of the IVD, demonstrating that inflammatory insults alone may potentially trigger degenerative changes of the IVD. SN - 1528-1159 UR - https://www.unboundmedicine.com/medline/citation/22850250/Toll_Like_Receptor_4__TLR4__expression_and_stimulation_in_a_model_of_intervertebral_disc_inflammation_and_degeneration_ L2 - http://dx.doi.org/10.1097/BRS.0b013e31826b71f4 DB - PRIME DP - Unbound Medicine ER -