Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Angiotensin II Type 1 Receptor Antagonist Losartan Inhibits TNF-α Induced Inflammation and Degeneration Processes in Human Nucleus Pulposus Cells

Babak Saravi
ORCID logo ,
Zhen Li
ORCID logo ,
Judith Pfannkuche
,
Laura Wystrach
,
Christoph E. Albers
,
Sibylle Grad
ORCID logo ,
Mauro Alini
,
R. Geoff Richards
ORCID logo ,
Corinna Lang
,
Norbert Südkamp
,
Hagen Schmal
ORCID logo ,
Gernot Lang
* ORCID logo
Version 1 : Received: 15 November 2020 / Approved: 17 November 2020 / Online: 17 November 2020 (14:48:38 CET)

A peer-reviewed article of this Preprint also exists.

Saravi, B.; Li, Z.; Pfannkuche, J.; Wystrach, L.; Häckel, S.; E. Albers, C.; Grad, S.; Alini, M.; Richards, R.G.; Lang, C.; Südkamp, N.; Schmal, H.; Lang, G. Angiotensin II Type 1 Receptor Antagonist Losartan Inhibits TNF-α-Induced Inflammation and Degeneration Processes in Human Nucleus Pulposus Cells. Appl. Sci. 2021, 11, 417. Saravi, B.; Li, Z.; Pfannkuche, J.; Wystrach, L.; Häckel, S.; E. Albers, C.; Grad, S.; Alini, M.; Richards, R.G.; Lang, C.; Südkamp, N.; Schmal, H.; Lang, G. Angiotensin II Type 1 Receptor Antagonist Losartan Inhibits TNF-α-Induced Inflammation and Degeneration Processes in Human Nucleus Pulposus Cells. Appl. Sci. 2021, 11, 417.

Abstract

Our recent study detected the expression of a tissue Renin-Angiotensin System (tRAS) in human intervertebral discs (IVDs). The present study sought to investigate the impact of angiotensin II receptor type 1 (AGTR1) antagonist losartan on human nucleus pulposus (NP) cell inflammation and degeneration induced by tumor necrosis factor-α (TNF-α). Human NP cells (4 donors, Pfirrmann grade 2-3, 30-37 years old, male) were isolated and expanded. TNF-α (10 ng/mL) was used to induce inflammation and degeneration. We examined the impact of losartan supplementation and measured gene expression of tRAS, anabolic, catabolic, and inflammatory markers in NP cells after 24 h and 72 h of exposure, respectively. T0070907, a PPAR-gamma antagonist, was applied to examine the regulatory pathway of losartan. Losartan (1 mM) significantly impaired TNF-α induced increase of pro-inflammatory (nitric oxide and TNF-α), catabolic (matrix metalloproteinases), and tRAS (AGTR1a and Angiotensin Converting Enzyme) markers. Further, losartan maintained the NP cell phenotype by upregulating aggrecan and downregulating collagen type I expression. In summary, losartan showed anti-inflammatory, anti-catabolic, and positive phenotype modulating effects on human NP cells. These results indicate that tRAS signaling plays an important role in IVD degeneration, and tRAS modulation with losartan could represent a novel therapeutic approach.

Keywords

Intervertebral Disc; Renin-Angiotensin-System; Degeneration; Regeneration; Spine; Inflammation

Subject

Medicine and Pharmacology, Immunology and Allergy

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.