Anti-inflammatory effects of FS48, the first potassium channel inhibitor from the salivary glands of the flea Xenopsylla cheopis

• DOI: 10.1016/j.jbc.2021.100670
• Publication Date: 2021-04-16T02:19:25Z
• Authors: Zhenhui Deng; Qingye Zeng; Jie Tang; Bei Zhang; Jinwei Chai; John F. Andersen; Xin Chen; Xueqing Xu
• Keywords: Proinflammatory cytokine; Xenopsylla

The voltage-gated potassium (Kv) 1.3 channel plays a crucial role in the immune responsiveness of T-lymphocytes and macrophages, presenting potential target for treatment immune- inflammation related-diseases. FS48, protein from rodent flea Xenopsylla cheopis, shares three disulfide bond feature scorpion toxins. However, its three-dimensional structure biological function are still unclear. In present study, FS48 was evaluated by circular dichroism homology modeling. We also described vitro ion activity using patch clamp recording investigated anti-inflammatory LPS-induced Raw 264.7 macrophage cells carrageenan-induced paw edema mice. found to adopt common αββ contain an atypical dyad motif. It dose-dependently exhibited Kv1.3 HEK 293T cells, ability block pore demonstrated kinetics activation competition binding with tetraethylammonium. downregulated secretion proinflammatory molecules NO, IL-1β, TNF-α, IL-6 manner dependent on blockage subsequent inactivation MAPK/NF-κB pathways. Finally, we observed that inhibited formation, tissue myeloperoxidase activity, inflammatory cell infiltrations carrageenan-treated therefore conclude identified saliva is novel inhibitor displaying activity. This discovery will promote understanding bloodsucking mechanism provide new template molecule design blockers.