Kir2.1 channel regulates macrophage polarization via the Ca2+/CaMK II/ERK/NF-κB signaling pathway.

Macrophage polarization plays a key role in the inflammatory response. Various ion channels expressed in macrophages have been documented, but very little is known about their roles in macrophage polarization. We found that knockdown or blockade of the Kir2.1 (also known as KCNJ2) channel significantly inhibited M1 macrophage polarization, but promoted M2 macrophage polarization. Lipopolysaccharide (LPS)-induced M1 polarization was also remarkably suppressed in high extracellular K+ solutions (70 mM K+), and this inhibition was partially abolished by adding Ca2+ to the culture medium. Ca2+ imaging showed that Ca2+ influx was dependent on the hyperpolarized membrane potential generated by the Kir2.1 channel. The upregulation of phospho (p)-CaMK II, p-ERK, and p-NF-κB proteins in macrophages from the RAW264.7 cell line that were stimulated with LPS was significantly reversed by blocking the Kir2.1 channel or culturing the cells with 70 mM K+ medium. Furthermore, in vivo studies showed that mice treated with a Kir2.1 channel blocker were protected from LPS-induced peritonitis. In summary, our data reveal the essential role of the Kir2.1 channel in regulating macrophage polarization via the Ca2+/CaMK II/ERK/NF-κB signaling pathway.

The effects of simmelian ties on innovation of low-carbon technology: a study of top managers' environmental awareness and stakeholder pressure in China.

Low-carbon technology innovation (LTI) engenders environmental protection and socioeconomic development. Hence, low-carbon innovation of enterprises becomes a crucial policy arena for national development and climate mitigation strategy. LTI is now associated with enhanced reputation and competitive edge of enterprises. We constructed a framework to empirically explore the impact of simmelian ties (ST) on LTI, testing the moderating effect of stakeholder pressure in this relationship. We used a sample of 385 employees from industrial enterprises in China through a structured questionnaire. The study results show that: first, when the enterprise is in a strong ST, the top managers' awareness of environmental benefits has a significant positive impact on LTI. Second, when the enterprise is in a weak ST, top managers' awareness of environmental risk has a significant positive impact on LTI. Third, pressure of key stakeholders and pressure of secondary stakeholders positively moderate the interaction between ST and top managers' environmental awareness (TMEA) on the impact of LTI. Fourth, the moderating effect of key stakeholders' pressure was observed to be stronger than that of secondary stakeholders' pressure. Theoretically, this paper contributes to literature by developing a framework to investigate interaction between ST, TMEA and LTI under different stakeholder pressures. Based on this framework, we provide a theoretical reference for enterprises to choose the appropriate and optimal TMEA for competitive edge.