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

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

doi:10.1371/journal.pone.0088174

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

PLoS One. 2014 Feb 7;9(2):e88174. doi: 10.1371/journal.pone.0088174. eCollection 2014.

Authors

Karina Furlani Zoccal¹, Claudia da Silva Bitencourt¹, Francisco Wanderley Garcia Paula-Silva¹, Carlos Artério Sorgi¹, Karla de Castro Figueiredo Bordon², Eliane Candiani Arantes², Lúcia Helena Faccioli¹

Affiliations

¹ Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
² Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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

Grants and funding

The authors are grateful to the São Paulo Research Foundation (FAPESP, grant # 2009/07169-5 and fellowship #2010/18179-9) and National Council for Scientific and Technological Development (CNPq). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.