TLR2, TLR4 and CD14 recognize venom-associated molecular patterns from Tityus serrulatus to induce macrophage-derived inflammatory mediators.

Abstract

Scorpion sting-induced human envenomation provokes an intense inflammatory reaction. However, the mechanisms behind the recognition of scorpion venom and the induction of mediator release in mammalian cells are unknown. We demonstrated that TLR2, TLR4 and CD14 receptors sense Tityus serrulatus venom (TsV) and its major component, toxin 1 (Ts1), to mediate cytokine and lipid mediator production. Additionally, we demonstrated that TsV induces TLR2- and TLR4/MyD88-dependent NF-κB activation and TLR4-dependent and TLR2/MyD88-independent c-Jun activation. Similar to TsV, Ts1 induces MyD88-dependent NF-κB phosphorylation via TLR2 and TLR4 receptors, while c-Jun activation is dependent on neither TLR2 nor TLR4/MyD88. Therefore, we propose the term venom-associated molecular pattern (VAMP) to refer to molecules that are introduced into the host by stings and are recognized by PRRs, resulting in inflammation.

• Authors: Karina Furlani Zoccal, Claudia da Silva Bitencourt, Francisco Wanderley Garcia Paula-Silva, Carlos Artério Sorgi, Karla de Castro Figueiredo Bordon, Eliane Candiani Arantes, Lúcia Helena Faccioli
• Journal: PloS one (PLoS One) Vol. 9 Issue 2 Pg. e88174 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24516606 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Inflammation Mediators
• Lipopolysaccharide Receptors
• NF-kappa B
• Scorpion Venoms
• Tlr2 protein, mouse
• Tlr4 protein, mouse
• Toll-Like Receptor 2
• Toll-Like Receptor 4
• tityustoxin

Topics

• Animals
• Inflammation Mediators (metabolism)
• Lipopolysaccharide Receptors (genetics, metabolism)
• Macrophage Activation (drug effects)
• Macrophages, Peritoneal (drug effects, metabolism)
• Mice
• Mice, Knockout
• NF-kappa B (metabolism)
• Phosphorylation (drug effects)
• Scorpion Venoms (pharmacology)
• Signal Transduction (drug effects)
• Toll-Like Receptor 2 (genetics, metabolism)
• Toll-Like Receptor 4 (genetics, metabolism)