Modulation of Voltage-Dependent and Inward Rectifier Potassium Channels by 15-Epi-Lipoxin-A4 in Activated Murine Macrophages: Implications in Innate Immunity

• DOI: 10.4049/jimmunol.1300235
• Publication Date: 2013-11-19T04:49:09Z
• Authors: Cristina Moreno; Patricia Prieto; Álvaro Macías; María Pimentel-Sa...; Alicia de la Cruz; Paqui G Través; Lisardo Boscá; Carmen Valenzuela
• Keywords: Lipoxin

Potassium channels modulate macrophage physiology. Blockade of voltage-dependent potassium (Kv) by specific antagonists decreases cytokine production and inhibits proliferation. In the presence aspirin, acetylated cyclooxygenase-2 loses activity required to synthesize PGs but maintains oxygenase produce 15R-HETE from arachidonate. This intermediate product is transformed via 5-LOX into epimeric lipoxins, termed 15-epi-lipoxins (15-epi-lipoxin A4 [e-LXA4]). Kv have been proposed as anti-inflammatory targets. Therefore, we studied effects e-LXA4 on signaling inward rectifier (Kir) in mice bone marrow-derived macrophages (BMDM). Electrophysiological recordings were performed these cells whole-cell patch-clamp technique. Treatment BMDM with inhibited LPS-dependent activation NF-κB IκB kinase β activity, protected against LPS activation-dependent apoptosis, enhanced accumulation Nrf-2 transcription factor. Moreover, treatment LPS-stimulated resulted a rapid decrease currents, compatible attenuation inflammatory response. Long-term significantly reverted Kir currents. Under conditions, decreased calcium influx versus that observed BMDM. These partially mediated lipoxin receptor (ALX), because they selective ALX antagonist. We provide evidence for new mechanism which contributes inflammation resolution, consisting reversion currents macrophages.