Abstract
Abstract Description
Brevetoxins are marine algal biotoxins present in warm coastal regions during red tide blooms and bind to and modulate voltage-gated sodium ion channel (VGSC) function on neuronal cells to confer their deleterious activity. In this study, we evaluate the effect of PbTx-2, the most prevalent type of brevetoxins produced during red tide blooms, on macrophage (RAW 264.7) inflammatory responses using ELISA, nitric oxide assay, as well as toxicity assays, and determine if VGSCs play a part in brevetoxin’s mechanism via patch-clamp analysis. Brevetoxin (< 2000 ng/mL) was not toxic to the macrophage cell line when incubated for as long as 24 hours. In addition, brevetoxin did not inhibit or enhanced the lipopolysaccharide (LPS) induction of nitric oxide as well as TNFa production by the RAW 264.7 macrophages. Brevetoxin did, however, stimulate TNFa production in the macrophages in a dose-dependent manner when incubated alone with the cells. Furthermore, brevetoxin inhibited LPS stimulation of IL-1 and IL-6. VGSCs are not expressed on the plasma membrane of RAW 264.7 macrophage cells in the naïve or LPS-activated state as no sodium ion current flow could be measured upon test pulse depolarizations in patch-clamp experiments. Thus, brevetoxin modulates inflammatory responses in RAW 264.7 mouse macrophages differentially, and these effects are not due to binding of brevetoxin to VGSCs on the surface of RAW 264.7 macrophage cells since sodium ion current could not be detected.
Funding Sources
Supported by the Holmes Development Funds Grant managed by Whitaker Center for STEM Education at Florida Gulf Coast University.
Topic Categories
Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)
