Snake and arthropod venoms: Search for inflammatory activity in human cells involved in joint diseases

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Alvarez-Flores, Miryam Paola ; Batista, Isabel de Fatima Correia ; Boas, Isadora Maria Villas ; Bufalo, Michelle Cristiane ; de Souza, Jean Gabriel ; Oliveira, Douglas Souza ; Bonfa, Giuliano ; Fernandes, Cristina Maria ; Porto, Rafael Marques ; Lichtenstein, Flavio ; Picolo, Gisele ; Tambourgi, Denise V. ; Chudzinski-Tavassi, Ana Marisa ; Ibanez, Olga Celia Martinez ; Teixeira, Catarina

• Document type: Journal article
• Source: Toxicon; v. 238, p. 14-pg., 2023-12-27.

Abstract

Most anti-inflammatory drugs currently adopted to treat chronic inflammatory joint diseases can alleviate symptoms but they do not lead to remission. Therefore, new and more efficient drugs are needed to block the course of joint inflammatory diseases. Animal venoms, rich in bioactive compounds, can contribute as valuable tools in this field of research. In this study, we first demonstrate the direct action of venoms on cells that constitute the articular joints. We established a platform consisting of cell-based assays to evaluate the release of cytokines (IL-6, IL-8, TNF alpha, IL-1 beta, and IL-10) by human chondrocytes, synoviocytes and THP1 macrophages, as well as the release of neuropeptides (substance-P and beta-endorphin) by differentiated sensory neuron-like cells, 24 h after stimulation of cells with 21 animal venoms from snake and arthropod species, sourced from different taxonomic families and geographic origins. Results demonstrated that at non-cytotoxic concentrations, the venoms activate at varying degrees the secretion of inflammatory mediators involved in the pathology of articular diseases, such as IL-6, IL-8, and TNF-alpha by chondrocytes, synoviocytes, and macrophages and of substance P by neuron-like cells. Venoms of the Viperidae snake family were more inflammatory than those of the Elapidae family, while venoms of Arthropods were less inflammatory than snake venoms. Notably, some venoms also induced the release of the antiinflammatory IL-10 by macrophages. However, the scorpion Buthus occitanus venom induced the release of IL10 without increasing the release of inflammatory cytokines by macrophages. Since the cell types used in the experiments are crucial elements in joint inflammatory processes, the results of this work may guide future research on the activation of receptors and inflammatory signaling pathways by selected venoms in these particular cells, aiming at discovering new targets for therapeutic intervention. (AU)

• FAPESP's process: 16/12128-0 - Pain in arthritis molecular mechanisms: identification of new targets for drug development
• Grantee: Michelle Cristiane Búfalo
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/13139-0 - Centre of Excellence in New Target Discovery
• Grantee: Ana Marisa Chudzinski-Tavassi
• Support Opportunities: Research Grants - Research Centers in Engineering Program
• FAPESP's process: 17/07009-4 - Signaling pathways involved in inflammatory response in osteoarthritis 3D culture models
• Grantee: Giuliano Bonfá
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/06736-0 - Identification/elucidation and validation of new targets/pathways involved in osteoarthritis
• Grantee: Jean Gabriel de Souza
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/50040-4 - Rational approach for searching molecular targets involved in inflammatory events and cell survival
• Grantee: Ana Marisa Chudzinski-Tavassi
• Support Opportunities: Research Grants - Research Centers in Engineering Program