Human Chondrocyte Activation by Toxins FromPremolis semirufa, an Amazon Rainforest Moth Caterpillar: Identifying an Osteoarthritis Signature

Author(s)

Villas-Boas, Isadora M. ^[1] ; Pidde, Giselle ^[1] ; Lichtenstein, Flavio ^[2] ; Ching, Ana Tung Ching ^[1] ; Meirelles Junqueira-de-Azevedo, Inacio De Loiola ^[3] ; DeOcesano-Pereira, Carlos ^[2] ; Madureira Trufen, Carlos Eduardo ^[2] ; Chudzinski-Tavassi, Ana Marisa ^[2] ; Pereira Morais, Katia Luciano ^[2] ; Tambourgi, V, Denise

Affiliation

^[1] V, Butantan Inst, Immunochem Lab, Sao Paulo - Brazil

^[2] Butantan Inst, Ctr Excellence New Target Discovery CENTD, Sao Paulo - Brazil

^[3] Butantan Inst, Ctr Toxins Immune Response & Cell Signaling CeTIC, Special Lab Appl Toxinol, Sao Paulo - Brazil

• Document type: Journal article
• Source: FRONTIERS IN IMMUNOLOGY; v. 11, SEP 18 2020.
• Web of Science Citations: 0

Abstract

Pararamosis is a disease that occurs due to contact with the hairs of the larval stage of the Brazilian mothPremolis semirufa. Envenomation induces osteoarticular alterations with cartilage impairment that resembles joint synovitis. Thus, the toxic venom present in the caterpillar hairs interferes with the phenotype of the cells present in the joints, resulting in inflammation and promoting tissue injury. Therefore, to address the inflammatory mechanisms triggered by envenomation, we studied the effects ofP.semirufahair extract on human chondrocytes. We have selected for the investigation, cytokines, chemokines, matrix metalloproteinases (MMPs), complement components, eicosanoids, and extracellular matrix (ECM) components related to OA and RA. In addition, for measuring protein-coding mRNAs of some molecules associated with osteoarthritis (OA) and rheumatoid arthritis (RA), reverse transcription (RT) was performed followed by quantitative real-time PCR (RT-qPCR) and we performed the RNA-sequencing (RNA-seq) analysis of the chondrocytes transcriptome. In the supernatant of cell cultures treated with the extract, we observed increased IL-6, IL-8, MCP-1, prostaglandin E2, metalloproteinases (MMP-1, MMP-2, MMP-3 and MMP-13), and complement system components (C3, C4, and C5). We noticed a significant decrease in both aggrecan and type II collagen and an increase in HMGB1 protein in chondrocytes after extract treatment. RNA-seq analysis of the chondrocyte transcriptome allowed us to identify important pathways related to the inflammatory process of the disease, such as the inflammatory response, chemotaxis of immune cells and extracellular matrix (ECM) remodeling. Thus, these results suggest that components ofPremolis semirufahair have strong inflammatory potential and are able to induce cartilage degradation and ECM remodeling, promoting a disease with an osteoarthritis signature. Modulation of the signaling pathways that were identified as being involved in this pathology may be a promising approach to develop new therapeutic strategies for the control of pararamosis and other inflammatory joint diseases. (AU)

• FAPESP's process: 13/50158-0 - Evaluation of bristles extract effects of Premolis semirufa, etiologic agent of pararamose, on human chondrocytes
• Grantee: Isadora Maria Villas Boas Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral