Regulation of Histone Acetylation During Inflammation Resolution

Inflammatory resolution is an active and coordinated process. Histone acetylation represents the primary epigenetic alteration associated with inflammatory diseases. However, the precise role of histone acetylation in the resolution of inflammation remains poorly understood.

Lipopolysaccharide (1 µg/mL, 10 ng/mL) and Escherichia coli (10⁵ c.f.u. 10⁶ c.f.u.) were employed to establish inflammatory models both in vitro and in vivo. UPLC-MS/MS was utilized to quantify acetyl CoA and lipid mediators. qPCR was conducted to assess the expression of specific genes. Flow cytometry analysis was performed to enumerate polymorphonuclear neutrophils and monocytes/macrophages. Histone acetylation was evaluated using Western blotting.

Our analysis reveals that histone acetylation and acetyl CoA are temporally regulated during the inflammatory response. A low-dose challenge results in heightened histone acetylation and reduced acetyl CoA. Metabolic repatterning during the inflammatory response promotes the generation of acetyl CoA and histone acetylation. Furthermore, the overexpression of histone acetylation enhances the production of anti-inflammatory lipid mediators, particularly the specialized pro-resolving lipid mediators (SPMs).

These findings illustrate that histone acetylation is not only temporally and differentially regulated during inflammatory responses but also interacts with metabolic reprogramming to promote the production of SPMs, thereby facilitating inflammation resolution.