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
Clicks: 170
ID: 143825
2014
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This
article has not been analysed, so there is no overall score —
reader engagement is measured and shown alongside.
Reader Engagement
Steady Performance
30.0
/100
170 views
19 readers
AI Quality Assessment
Not analyzed
Readership in this journal
SteadyRanked #232 of 394 articles by views in macromolecular bioscience
Most read
Least read
Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 394 in total.
Mint this article as an NFT
Not yet mintedCreate a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.
5
SUSD
one-off · no wallet required
Abstract
The Ca2+-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 the healthy and damaged CNS—and that KCa3.1 contributes to P2Y2 receptor-stimulated migration. Here, we discovered that KCa3.1 is greatly increased in alternative-activated rat microglia and then contributes to an enhanced migratory capacity. IL-4 up-regulated KCNN4 mRNA (by 6 hr) and greatly increased the KCa3.1 current by 1 day, and this required de novo protein synthesis. The increase in current was sustained for at least 6 days. IL-4 increased microglial migration and this was reversed by blocking KCa3.1 with TRAM-34. A panel of inhibitors of signal-transduction mediators was used to analyze contributions of IL-4-related signaling pathways. Induction of KCNN4 mRNA and KCa3.1 current was mediated specifically through IL-4 binding to the type I receptor and, surprisingly, it required JAK3, Ras/MEK/ERK signaling and the transcription factor, AP-1, rather than JAK2, STAT6 or PI3K. The same receptor subtype and pathway were required for the enhanced KCa3.1-dependent migration. In providing the first direct signaling link between an IL-4 receptor, expression and roles of an ion channel, this study also highlights the potential importance of KCa3.1 in alternative-activated microglia.
| Reference Key |
eferreira2014frontiersil-4
Use this key to autocite in the manuscript while using
SciMatic Manuscript Manager or Thesis Manager
|
|---|---|
| Authors | ;Roger eFerreira;Roger eFerreira;Starlee eLively;Lyanne eSchlichter;Lyanne eSchlichter |
| Journal | macromolecular bioscience |
| Year | 2014 |
| DOI |
10.3389/fncel.2014.00183
|
| URL | |
| Keywords |
Citations
No citations found. To add a citation, contact the admin at info@scimatic.org
Comments
No comments yet. Be the first to comment on this article.