Treatment with Melittin Induces Apoptosis and Autophagy of Fibroblastlike Synoviocytes in Patients with Rheumatoid Arthritis

Curr Pharm Biotechnol. 2020;21(8):734-740. doi: 10.2174/1389201021666191210110826.

Abstract

Background: Melittin, the major medicinal component of honeybee venom, exerts antiinflammatory, analgesic, and anti-arthritic effects in patients with Rheumatoid Arthritis (RA). RA is an inflammatory autoimmune joint disease that leads to irreversible joint destruction and functional loss. Fibroblast-Like Synoviocytes (FLS) are dominant, special mesenchymal cells characterized by the structure of the synovial intima, playing a crucial role in both the initiation and progression of RA.

Objective: In this study, we evaluated the effects of melittin on the viability and apoptosis of FLS isolated from patients with RA.

Methods: Cell viability was determined using CCK-8 assays; apoptosis was evaluated by flow cytometry, and the expression levels of apoptosis-related proteins (caspase-3, caspase-9, BAX, and Bcl-2) were also determined. To explore whether melittin alters inflammatory processes in RA-FLS, IL-1β levels were determined using an enzyme-linked immunosorbent assay (ELISA). Furthermore, we performed GFP-LC3 punctate fluorescence dot assays and western blotting (for LC3, ATG5, p62, and Beclin 1) to assess autophagy in RA-FLS.

Results: Our results show that melittin can significantly impair viability, promote apoptosis and autophagy, and inhibit IL-1β secretion in RA-FLS.

Conclusion: Melittin may be useful in preventing damage to the joints during accidental local stimulation.

Keywords: ELISA; Melittin; apoptosis; autophagy; fibroblast-like synoviocytes; rheumatoid arthritis.

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / pathology*
  • Autophagy / drug effects*
  • Caspase 3 / metabolism
  • Cell Survival / drug effects
  • Cells, Cultured
  • Fibroblasts / drug effects*
  • Fibroblasts / immunology
  • Fibroblasts / pathology
  • Humans
  • Interleukin-1beta / metabolism
  • Melitten / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Synoviocytes / drug effects*
  • Synoviocytes / immunology
  • Synoviocytes / pathology

Substances

  • Apoptosis Regulatory Proteins
  • BCL2 protein, human
  • IL1B protein, human
  • Interleukin-1beta
  • Proto-Oncogene Proteins c-bcl-2
  • Melitten
  • CASP3 protein, human
  • Caspase 3