Investigating the anti-inflammatory potential of losartan and its pathway on human and bovine nucleus pulposus cells

Abstract: We hypothesized, that by blocking the action of angiotensin II on its main receptor AGTR1, markers of inflammation and degeneration on gene and protein levels could be reduced in human and bovine nucleus pulposus cells. Inflammation is thought to play a central role in the progression towards symptomatic disc disease, a disease with a huge socio-economic impact. The tRAS system has been first discovered and subsequently connected to inflamed human intervertebral disc tissue in previous experiments of the group. Healthy human and bovine nucleus pulposus cells (NPc) were isolated and expanded in cell monolayers under standard culture conditions. Inflammation was induced by the addition of human recombinant TNF-α 10 ng/mL. Losartan 100µM and 1000µM were added as treatment. Our hypothesis of the anti inflammatory and anti-degenerative action of losartan could be confirmed in human and bovine NP cells. Even though markers of inflammation and degeneration were downregulated in both bovine and human NP cells after treatment with high dose losartan, tRAS markers were only significantly induced in human NP cells. Our search for a potent inflammation and tRAS inducer in bovine NP cells yielded important results on inflammation induction, however, the tRAS system was non-reactive to inflammatory stimuli with bovine recombinant TNF α (10 ng/mL), bovine recombinant interleukin-1β (IL-1β) 10 ng/mL, bovine recombinant Interferon-α (IFN-α) 10 ng/mL and 10µg/mL lipopolysaccharide (LPS) from E. coli. The anti-inflammatory and anti degenerative effect of losartan was evident in both human as well as bovine NP cells, thus we hypothesized that this effect may be at least partially via other receptors. Losartan's PPARγ agonism as an anti-inflammatory mediator came into focus here. This hypothesis was confirmed, as losartan's afromentioned effect on human NP cells could be partially reversed by the PPARγ blocker T0070907. In conclusion, a significant anti-inflammatory and anti-degenerative effect of 1000 µM losartan on human and bovine NP cells were observed. Losartan induced, under inflammatory conditions, anabolic markers like aggrecan and showed an NP cell preserving effect by downregulation of collagen I. Finally, we could show, that losartan exerts these effects not only via its well-known antagonism on AGTR1 but also via agonism on the PPARγ receptor. Follow-up studies may investigate losartan's effect on a tissue level and may investigate the most efficient way of application in anticipation of a clinical use

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Universität Freiburg, Dissertation, 2024

Klassifikation und Themen

• Schlagwort: Entzündung ; Bandscheibe ; Bandscheibendegeneration ; Chronischer Schmerz ; Degeneration ; Anabolismus ; Renin-Angiotensin-System ; Antiphlogistikum ; Orthopädie ; Spine

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2024
• Urheber: Pfannkuche, Judith-Johanna
• Beteiligte Personen und Organisationen: Südkamp, Norbert P. ; Lang, Gernot Michael ; Fink, Jodok Matthias ; Klinik für Orthopädie und Unfallchirurgie. Freiburg im Breisgau ; Albert-Ludwigs-Universität Freiburg. Medizinische Fakultät

Weitere Informationen

• DOI: 10.6094/UNIFR/258555
• URN: urn:nbn:de:bsz:25-freidok-2585553
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 15.08.2025, 07:23 MESZ