AUTHOR=Liu Kaiwen , Wei Jianlu , Li Guohua , Liu Ronghan , Zhao Dawang , Zhang Yuanqiang , Shi Jie , Xie Qing , Cheng Lei 

TITLE=Fexofenadine Protects Against Intervertebral Disc Degeneration Through TNF Signaling

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.687024

DOI=10.3389/fcell.2021.687024

ISSN=2296-634X

ABSTRACT=<p><bold>Objective:</bold> Fexofenadine (FFD) is an antihistamine drug with an anti-inflammatory effect. The intervertebral disc (IVD) degeneration process is involved in inflammation in which tumor necrosis factor-α (TNF-α) plays an important role. This study aims to investigate the role of FFD in the pathological process of IVD degeneration.</p><p><bold>Methods:</bold> Safranin O staining was used for the measurement of cartilageous tissue in the disc. Hematoxylin-Eosin (H&amp;E) staining was used to determine the disc construction. A rat needle puncture model was taken advantage of to examine the role of FFD in disc degeneration <italic>in vivo</italic>. Western Blotting assay, immunochemistry, and immunoflurence staining were used for the determination of inflammatory molecules. ELISA assay was performed to detect the release of inflammatory cytokines. A real-time PCR assay was analyzed to determine the transcriptional expressions of molecules.</p><p><bold>Results:</bold> Elevated TNF-α resulted in inflammatory disc degeneration, while FFD protected against TNF-α-induced IVD degeneration. Mechanism study found FFD exhibited a disc protective effect through at least two pathways. (a) FFD inhibited TNF-α-mediated extracellular matrix (ECM) degradation and (b) FFD rescued TNF-α induced inflammation in disc degeneration. Furthermore, the present study found that FFD suppressed TNF-α mediated disc degeneration via the cPLA2/NF-κB signaling pathway.</p><p><bold>Conclusions:</bold> FFD provided another alternative for treating disc degeneration through a novel mechanism. Additionally, FFD may also be a potential target for the treatment of other inflammatory-related diseases, including IVD degeneration.</p>