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

Chang-Lun Huang; Der-Yuan Chen; Chih-Chen Tzang; Jhen-Wei Lin; Bor-Show Tzang; Tsai-Ching Hsu

doi:10.3892/mmr.2023.13080

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

Mol Med Rep. 2023 Oct;28(4):193. doi: 10.3892/mmr.2023.13080. Epub 2023 Sep 1.

Authors

Chang-Lun Huang¹, Der-Yuan Chen², Chih-Chen Tzang³, Jhen-Wei Lin², Bor-Show Tzang², Tsai-Ching Hsu²

Affiliations

¹ Division of Thoracic Surgery, Department of Surgery, Changhua Christian Medical Foundation Changhua Christian Hospital, Changhua 500, Taiwan, R.O.C.
² Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan, R.O.C.
³ School of Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan, R.O.C.

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.

Keywords: celastrol; human parvovirus B19; inflammasome; inflammation; macrophages; non‑structural protein 1.

MeSH terms

Arthritis, Rheumatoid*
Cytokines
Humans
Inflammasomes
Macrophages
NLR Family, Pyrin Domain-Containing 3 Protein
Parvovirus B19, Human*

Substances

celastrol
Inflammasomes
NLR Family, Pyrin Domain-Containing 3 Protein
Cytokines

Grants and funding

This study was supported by Chung Shan Medical University and Changhua Christian Hospital cooperative project (grant no. CSMU‑CCH‑110‑02) and in part by The Ministry of Science and Technology, Taiwan (grant nos. MOST 108-2314-B-040-018 and 109-2314-B040-021, and NSTC 112-2314-B040-015).