The matricellular protein SPARC induces inflammatory interferon-response in macrophages during aging

SPARC is a member of matricellular protein, and emerging evidence suggests that it plays a critical role in integrated metabolic and inflammatory responses. However, the mechanism how SPARC activates inflammation is still unanswered. Here we showed that excess SPARC induced sterile inflammation, and converted anti-inflammatory macrophage to pro-inflammatory macrophage. RNA-sequencing analysis revealed that SPARC elicits interferon-stimulated genes (ISGs) by transcription factor IRF7. SPARC also dampened mitochondrial respiration that induced pro-glycolytic inflammatory macrophage. Altogether, we discovered a mechanism how SPARC triggers sterile inflammatory response in anti-inflammatory macrophage, and this implicates the potential role of SPARC as a modulator of anti-inflammatory macrophages to maintain tissue homeostasis. Overall design: Examination of RNA expression changes in mouse peritoneal macrophages from thioglycollate (TG) injected or IL-4 complex (IL4) injected mice, with or without treatment of SPARC ex vivo.