Ulinastatin Ameliorates IL‐1β‐Induced Cell Dysfunction in Human Nucleus Pulposus Cells via Nrf2/NF‐κB Pathway

Abstract

Low back pain (LBP) has been a wide public health concern worldwide. Among the pathogenic factors, intervertebral disc degeneration (IDD) has been one of the primary contributors to LBP. IDD correlates closely with inflammatory response and oxidative stress, involving a variety of inflammation-related cytokines, such as interleukin 1 beta (IL-1β), which could result in local inflammatory environment. Ulinastatin (UTI) is a kind of acidic protein extracted from human urine, which inhibits the release of tumor necrosis factor alpha (TNF-α) and other inflammatory factors to protect organs from inflammatory damage. However, whether this protective effect of UTI on human nucleus pulposus (NP) exists, and how UTI affects the biological behaviors of human NP cells during IDD remain elusive. In this current study, we revealed that UTI could improve the viability of NP cells and promote the proliferation of NP cells. Additionally, UTI could protect human NP cells via ameliorating IL-1β-induced apoptosis, inflammatory response, oxidative stress, and extracellular matrix (ECM) degradation. Molecular mechanism analysis suggested that the protective effect from UTI on IL-1β-treated NP cells were through activating nuclear factor- (erythroid-derived 2-) like 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway and the suppression of NF-κB signaling pathway. Therefore, UTI may be a promising therapeutic medicine to ameliorate IDD.

Tissue Renin‐Angiotensin System (tRAS) Induce Intervertebral Disc Degeneration by Activating Oxidative Stress and Inflammatory Reaction

“…This method has been reported in our recent study [ 2 ]. Briefly, the collected intervertebral disc tissue was transported to laboratory using 0.9% sterile saline within two hours.…”

“…This method has been described in previous study [ 2 ]. After acquisition of mRNA from NP cells, total mRNA (100 ng/ μ L) was reversed using HiScript ® III RT SuperMix for qPCR Kit (R323-01, Vazyme, Nanjing, China).…”

“…This method has been described previously [ 2 ]. Intervertebral disc samples were sectioned, embedded with paraffin, and deparaffinized, followed by blocking the endogenous peroxide using 3% hydrogen peroxide.…”

“…Our previous study also described this method in detailly [ 2 ]. After intervertebral disc sections or NP cells were well prepared, 0.1% Triton X-100 was employed to permeate samples for 5 min.…”

“…Of the massive pathogenic factors, lumbar intervertebral disc degeneration (IDD) has been the mostly studied. Anatomically, the normal intervertebral disc is consist of gel-like inner nucleus pulposus tissue (NP), surrounding annulus fibrosus tissue (AF), and cartilaginous endplates structure (EP), which connects adjacently superior and inferior vertebral bodies [ 2 , 3 ]. In general, IDD is an age-related biological process.…”