Peptides ToAP3 and ToAP4 decrease release of inflammatory cytokines through TLR-4 blocking

Area of Science:

• Immunology
• Pharmacology
• Microbiology

Background:

• Antimicrobial peptides (AMPs) are crucial for innate immunity, exhibiting both microbicidal and immunomodulatory functions.
• The venom of the Brazilian scorpion Tityus obscurus is a source of bioactive molecules with therapeutic potential.
• Understanding the specific activities of AMPs like ToAP3 and ToAP4 is key to developing novel treatments.

Purpose of the Study:

• To investigate the anti-inflammatory and antimicrobial properties of ToAP3 and ToAP4, AMPs isolated from Tityus obscurus scorpion venom.
• To elucidate the mechanisms underlying their immunomodulatory effects on immune cells.
• To assess their efficacy against specific microbial pathogens.

Main Methods:

• Murine bone marrow-derived macrophages (BMDMs) and dendritic cells (BMDCs) were stimulated with peptides and lipopolysaccharide (LPS).
• Cytokine levels (TNF-α, IL-1β) and phenotypic markers (MHC-II, CD80, CD86) were analyzed.
• Antimicrobial activity was tested against Cryptococcus neoformans and Mycobacterium massiliense.

Main Results:

• Both peptides reduced pro-inflammatory cytokine transcript and protein levels (TNF-α, IL-1β) in BMDMs and BMDCs.
• Reduced TNF-α secretion correlated with peptide interaction with Toll-like receptor 4 (TLR-4).
• ToAP4 enhanced MHC-II expression, while ToAP3 decreased CD80/CD86 expression on BMDCs. Only ToAP3 demonstrated potent direct antimicrobial activity against M. massiliense.

Conclusions:

• ToAP3 and ToAP4 exhibit significant anti-inflammatory effects, modulating immune cell responses and cytokine production.
• The peptides show potential as immunomodulatory agents, with ToAP3 also demonstrating direct antibacterial action.
• These findings highlight AMPs from Tityus obscurus venom as promising candidates for developing new immunomodulatory and antibacterial therapies.