Tannic acid, an IL-1β-direct binding compound, ameliorates IL-1β-induced inflammation and cartilage degradation by hindering IL-1β-IL-1R1 interaction

Interleukin-1 beta (IL-1 beta) is one of the most potent pro-inflammatory cytokines implicated in a wide range of autoinflammatory, autoimmune, infectious, and degenerative diseases. Therefore, many researchers have focused on developing therapeutic molecules that inhibit IL-1 beta-IL-1 receptor 1 (IL-1R1) interaction for the treatment of IL-1-related diseases. Among IL-1-related diseases, osteoarthritis (OA), is characterized by progressive cartilage destruction, chondrocyte inflammation, and extracellular matrix (ECM) degradation. Tannic acid (TA) has been proposed to have multiple beneficial effects, including anti-inflammatory, anti-oxidant, and anti-tumor activities. However, it is unclear whether TA plays a role in anti-IL-1 beta activity by blocking IL-1 beta-IL-1R1 interaction in OA. In this study, we report the anti-IL-1 beta activity of TA in the progression of OA in both in vitro human OA chondrocytes and in vivo rat OA models. Herein, using-ELISA-based screening, natural compound candidates capable of inhibiting the IL-1 beta-IL-1R1 interaction were identified. Among selected candidates, TA showed hindering IL-1 beta-IL-1R1 interaction by direct binding to IL-1 beta using surface plasmon resonance (SPR) assay. In addition, TA inhibited IL-1 beta bioactivity in HEK-Blue IL-1-dependent reporter cell line. TA also inhibited IL-1 beta-induced expression of inducible nitric oxide synthase (NOS2), cyclooxygenase-2 (COX-2), IL-6, tumor necrosis factor-alpha (TNF-alpha), nitric oxide (NO), and prostaglandin E2 (PGE2) in human OA chondrocytes. Moreover, TA downregulated IL-1 beta-stimulated matrix metalloproteinase (MMP)3, MMP13, ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)4, and ADAMTS5, while upregulating collagen type II (COL2A1) and aggrecan (ACAN). Mechanistically, we confirmed that TA suppressed IL-1 beta-induced MAPK and NF-kappa B activation. The protective effects of TA were also observed in a monosodium iodoacetamide (MIA)-induced rat OA model by reducing pain and cartilage degradation and inhibiting IL-1 beta-mediated inflammation. Collectively, our results provide evidence that TA plays a potential role in OA and IL-1 beta-related diseases by hindering IL-1 beta-IL-1R1 interaction and suppressing IL-1 beta bioactivity.

Automated summary

The study revealed that tannic acid (TA) inhibits IL-1 beta-induced inflammation and matrix degradation in human OA chondrocytes by blocking IL-1 beta-IL-1R1 interaction. In addition, TA showed protective effects in a rat OA model by reducing pain, cartilage degradation, and IL-1 beta-mediated inflammation.