, 2000). The amino acid sequences were retrieved from the Universal Protein Resource Knowledgebase (www.uniprot.org) or the Worldwide Protein Data Bank (www.pdb.org). Ts2 (Uniprot ID P68410) contains 62 amino acids, including 8 cysteine BMS-754807 in vitro residues ( Mansuelle et al., 1992). The peptide has a theoretical molar mass of 6998.0 Da and a pI of 7.70 (http://web.expasy.org/protparam/). Ts2 is a sodium channel inhibitor α-neurotoxin that

inhibits the rapid inactivation of NaV1.2, NaV1.3, NaV1.5, NaV1.6 and NaV1.7, but does not affect NaV1.4, NaV1.8 or DmNaV1 ( Cologna et al., 2012). The overall structure of the Ts2 model consists of three β-strands and one α-helix that are arranged in a triangular shape forming a cysteine-stabilized α-helix ⁄ β-sheet (CSαβ) motif ( Cologna et al., 2012). While Ts6, also called TsTX-IV ( Arantes et al., 1989), acts on K+ channels ( Coronas et al., 2003). Ts6 (Uniprot ID P59936) contains 40 amino acids, including 8 cysteine residues ( Pimenta et al., 2003).

The theoretical molar mass and pI of the peptide are 4514.2 Da and 8.50, respectively (http://web.expasy.org/protparam/). Ts6 is a potassium channel toxin alpha-KTx 12.1 that inhibits high conductance calcium-activated potassium channels ( Novello et al., 1999) and weakly inhibits Shaker B potassium channels ( Coronas et al., 2003). The structure of the peptide consists of an alpha-helix connected to a triple-stranded beta-sheet stabilized by four disulfide bonds ( Oyama et al., 2005). Selleckchem Obeticholic Acid Our group has previously demonstrated that following stimulation with Ts1, Ts2 or Ts6, the in vitro release Unoprostone of inflammatory mediators by peritoneal macrophages (J774.1) is independent of the action of these toxins on ion channels ( Zoccal et al., 2011). Several reports demonstrated that cytokines are increased after envenomation. Magalhães et al. (1999) observed an increase of interleukins (IL)-1α, IL-6, Interferon (IFN)-γ and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the serum of patients who were stung by T. serrulatus. Furthermore, the increased

levels of GM-CSF in severe envenomation might be involved in neutrophilia induced by T. serrulatus venom ( Magalhães et al., 1999). The synthesis of anti-inflammatory cytokines, such as IL-10, was also observed in the plasma of patients with both moderate and severe cases of envenomation ( Fukuhara et al., 2003; Petricevich, 2010). Scorpion venoms can stimulate the immune-neuroendocrine axis by inducing the release of catecholamines, corticosteroids, bradykinin ( Chaudry et al., 1989; Sofer et al., 1996; Magalhães et al., 1999; Pessini et al., 2003) and eicosanoids mediators, such as prostaglandin (PG)E2, lipoxin A2 (LXA2) and leukotriene (LT)B4 ( Nascimento et al., 2005; Teixeira et al., 1997).