1. Mitochondrial cardiolipin plays a key role in macrophage inflammasome activation in response to apoptotic mitochondria.
Mitochondrial cardiolipin plays a key role in macrophage inflammasome activation in response to apoptotic mitochondria. LPS-primed J774A.1 cells were treated with mitochondria (100 mg/ml) under various conditions to determine which mitochondrial-derived molecules were responsible for inducing IL-1β production. (A) Neither heating mitochondria (100°C for 5 min) nor freezing mitochondria for (−80°C for 2 h) affected IL-1β production. (B) Separating mitochondria from J744A.1 macrophages with a 0.4-mM filter significantly reduced IL-1β production. (C) Treatment with an antioxidant (MitoTEMPO), an ATPase (apyrase), or DNase had no significant effect on IL-1β production. (D) Following lipid extraction with chloroform, the chloroform fraction retained the majority of the IL-1β stimulation substance, suggesting involvement of a lipid. (E) Inhibition of cardiolipin synthesis with palmitate prior to the induction of apoptosis significantly decreased cardiolipin levels in mitochondrial preparations, compared with oleate (negative control). (F) Mitochondria purified from cells pretreated with palmitate prior to induction of apoptosis induced significantly lower IL-1β production, compared with oleate (negative control). Comparisons were performed using a Kruskal–Wallis with Dunn multiple comparison test. A p value <0.05 was considered significant.
Minghua Zhu et al. ImmunoHorizons 2018;2:
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