Celastrol attenuates human parvovirus B19 NS1‑induced NLRP3 inflammasome activation in macrophages

Abstract

Human parvovirus B19 (B19V) has been strongly associated with a variety of inflammatory disorders, such as rheumatoid arthritis (RA), inflammatory bowel disease and systemic lupus erythematosus. non-structural protein 1 (nS1) of B19V has been demonstrated to play essential roles in the pathological processes of B19V infection due to its regulatory properties on inflammatory cytokines. Celastrol, a quinone methide isolated from Tripterygium wilfordii, has displayed substantial potential in treating inflammatory diseases, such as psoriasis and RA. However, little is known about the effects of celastrol on B19V NS1-induced inflammation. Therefore, cell viability assay, migration assay, phagocytosis analysis, zymography assay, eliSa and immunoblotting were conducted to verify the influences of celastrol on macrophages. The present study reported the attenuating effects of celastrol on B19V NS1-induced inflammatory responses in macrophages derived from human acute monocytic leukemia cell lines, U937 and THP-1. Although the migration was not significantly decreased by celastrol in both U937 and THP-1 macrophages, significantly decreased viability, migration and phagocytosis were detected in both B19V NS1-activated U937 and THP-1 macrophages in the presence of celastrol. Additionally, celastrol significantly decreased MMP-9 activity and the levels of inflammatory cytokines, including IL-6, TNF-α and il-1β, in B19V NS1-activated U937 and THP-1 cells. Notably, significantly decreased levels of nlr family pyrin domain-containing 3, apoptosis-associated speck-like, caspase-1 and IL-18 proteins were observed in both B19V NS1-activated U937 and THP-1 cells in the presence of celastrol, indicating the involvement of the inflammasome pathway. To the best of our knowledge, the present study is the first to report on the attenuating effects of celastrol on B19V NS1-induced inflammatory responses in macrophages, suggesting a therapeutic role for celastrol in B19V NS1-related inflammatory diseases.

The NLRP3 Inflammasome as a Pathogenic Player Showing Therapeutic Potential in Rheumatoid Arthritis and Its Comorbidities: A Narrative Review

“…Celastrol, a natural product isolated from Tripterygium wilfordii , has displayed therapeutic potential in inflammatory diseases, such as RA. One recent study showed the attenuating effects of celastrol on parvovirus B19-NS1-induced NLRP3 inflammasome activation in macrophages [ 132 ]. Jing et al also revealed that celastrol inhibited inflammation by inhibiting the reactive oxygen species NF-κB-NLRP3 inflammasome axis and relieved RA symptoms [ 133 ].…”