IL-4 type 1 receptor signaling up-regulates KCNN4 expression, and increases the KCa3.1 current and its contribution to migration of alternative-activated microglia.

ABSTRACT: The Ca(2+)-activated K(+) channel, KCa3.1 (KCNN4/IK1/SK4), contributes to "classical," pro-inflammatory activation of microglia, and KCa3.1 blockers have improved the outcome in several rodent models of CNS damage. For instance, blocking KCa3.1 with TRAM-34 rescued retinal ganglion neurons after optic nerve damage in vivo and, reduced p38 MAP kinase activation, production of reactive oxygen and nitrogen species, and neurotoxicity by microglia in vitro. In pursuing the therapeutic potential of KCa3.1 blockers, it is crucial to assess KCa3.1 contributions to other microglial functions and activation states, especially the IL-4-induced "alternative" activation state that can counteract pro-inflammatory states. We recently found that IL-4 increases microglia migration - a crucial function in t

SUBMITTER: Ferreira R 

PROVIDER: S-EPMC4077126 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature