P300/CBP‐associated factor (PCAF) attenuated M1 macrophage inflammatory responses possibly through KLF2 and KLF4

Abstract Macrophages exhibit distinct phenotypes in response to environmental signals. The polarization of M1 macrophages plays an essential role in the inflammatory response. However, the specific molecular mechanisms regulating the inflammatory response during M1 macrophage polarization remain to be further understood. Here, we found that the histone acetyltransferase P300/CBP‐associated factor (PCAF) was a potential negative regulator of the M1 macrophage inflammatory response. During M1 macrophage polarization, the inflammatory response gradually reduced, but PCAF expression increased. Furthermore, the overexpression of PCAF significantly inhibited the expression of the M1 macrophage‐related pro‐inflammatory genes TNF‐α, IL‐6 and CXCL10, while PCAF deficiency enhanced the expression of these genes. Furthermore, we found that PCAF overexpression suppressed the NF‐κB signaling pathway and promoted the expression of the Krüppel‐like factors (KLF) KLF2 and KLF4 through regulating their transcriptional levels. In addition, KLF2 and KLF4 deficiency reversed the PCAF‐induced inhibition of the expression of pro‐inflammatory genes in M1 macrophages. Collectively, the present results demonstrate a potential negative regulatory mechanism of the inflammatory response during M1 macrophage polarization and propose a novel mechanism of inflammation resolution for maintaining homeostasis.