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PLCL1 regulates fibroblast-like synoviocytes inflammation via NLRP3 inflammasomes in rheumatoid arthritis
Luo, Shuai; Li, Xiao-Feng; Yang, Ying-Li; Song, Biao; Wu, Sha; Niu, Xue-Ni; Wu, Yuan-Yuan; Shi, Wen; Huang, Cheng; Li, Jun.
  • Luo, Shuai; Anhui Medical University. School of Pharmacy. Anhui Institute of Innovative Drugs. Hefei. CN
  • Li, Xiao-Feng; Anhui Medical University. School of Pharmacy. Anhui Institute of Innovative Drugs. Hefei. CN
  • Yang, Ying-Li; Anhui Medical University. School of Pharmacy. Anhui Institute of Innovative Drugs. Hefei. CN
  • Song, Biao; The First Affiliated Hospital of Anhui Medical University. Department of Pharmacy. Hefei. CN
  • Wu, Sha; Anhui Medical University. School of Pharmacy. Anhui Institute of Innovative Drugs. Hefei. CN
  • Niu, Xue-Ni; Anhui Medical University. School of Pharmacy. Anhui Institute of Innovative Drugs. Hefei. CN
  • Wu, Yuan-Yuan; Anhui Medical University. School of Pharmacy. Anhui Institute of Innovative Drugs. Hefei. CN
  • Shi, Wen; Anhui Medical University. School of Pharmacy. Anhui Institute of Innovative Drugs. Hefei. CN
  • Huang, Cheng; Anhui Medical University. School of Pharmacy. Anhui Institute of Innovative Drugs. Hefei. CN
  • Li, Jun; Anhui Medical University. School of Pharmacy. Anhui Institute of Innovative Drugs. Hefei. CN
Adv Rheumatol ; 62: 25, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1383510
ABSTRACT
Abstract

Background:

Phospholipase C-like 1 (PLCL1), a protein that lacks catalytic activity, has similar structures to the PLC family. The aim of this research was to find the function and underlying mechanisms of PLCL1 in fibroblast-like synoviocyte (FLS) of rheumatoid arthritis (RA).

Methods:

In this study, we first analyzed the expression of PLCL1 in the synovial tissue of RA patients and K/BxN mice by immunohistochemical staining. Then silencing or overexpressing PLCL1 in FLS before stimulating by TNF-α. The levels of IL-6, IL-1β and CXCL8 in FLS and supernatants were detected by Western Blot (WB), Real-Time Quantitative PCR and Enzyme Linked Immunosorbent Assay. We used INF39 to specifically inhibit the activation of NLRP3 inflammasomes, and detected the expression of NLRP3, Cleaved Caspase-1, IL-6 and IL-1β in FLS by WB.

Result:

When PLCL1 was silenced, the level of IL-6, IL-1β and CXCL8 were down-regulated. When PLCL1 was overexpressed, the level of IL-6, IL-1β and CXCL8 were unregulated. The previous results demonstrated that the mechanism of PLCL1 regulating inflammation in FLS was related to NLRP3 inflammasomes. INF39 could counteract the release of inflammatory cytokines caused by overexpression of PLCL1.

Conclusion:

Result showed that the function of PLCL1 in RA FLS might be related to the NLRP3 inflammasomes. We finally confirmed our hypothesis with the NLRP3 inhibitor INF39. Our results suggested that PLCL1 might promote the inflammatory response of RA FLS by regulating the NLRP3 inflammasomes.


Full text: Available Index: LILACS (Americas) Language: English Journal: Adv Rheumatol Journal subject: Artrite / Reumatologia Year: 2022 Type: Article / Project document Affiliation country: China Institution/Affiliation country: Anhui Medical University/CN / The First Affiliated Hospital of Anhui Medical University/CN

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Full text: Available Index: LILACS (Americas) Language: English Journal: Adv Rheumatol Journal subject: Artrite / Reumatologia Year: 2022 Type: Article / Project document Affiliation country: China Institution/Affiliation country: Anhui Medical University/CN / The First Affiliated Hospital of Anhui Medical University/CN