Perivascular Stem Cells Suppress Inflammasome Activation during Inflammatory Responses in Macrophages
- Author:
Jeeyoung KIM
1
;
Woo Jin KIM
;
Kwon Soo HA
;
Eun Taek HAN
;
Won Sun PARK
;
Se Ran YANG
;
Seok Ho HONG
Author Information
- Publication Type:Original Article
- Keywords: Perivascular stem cells; Inflammation; Inflammasome; Macrophage
- MeSH: Animals; Biological Factors; Bone Marrow; Endoplasmic Reticulum Stress; Humans; Inflammasomes; Inflammation; Macrophages; Macrophages, Peritoneal; Mesenchymal Stromal Cells; Mice; Peritonitis; Plasminogen Activator Inhibitor 1; Reactive Oxygen Species; Stem Cells
- From:International Journal of Stem Cells 2019;12(3):419-429
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND AND OBJECTIVES: Perivascular stem cells (PVCs) have been identified as precursors of mesenchymal stem cells (MSCs) that offer promising prospects for application in the development of cellular therapies. Although PVCs have been demonstrated to have greater therapeutic potential compared to bone marrow and adipose tissue-derived MSCs in various diseases, the regulatory role of PVCs on inflammasome activation during macrophage-mediated inflammatory responses has not been investigated.METHODS AND RESULTS: In this study, we found that the PVC secretome effectively alleviates secretion of both caspase-1 and interleukin-1β in lipopolysaccharide-primed and activated human and murine macrophages by blocking inflammasome activation and attenuating the production of mitochondrial reactive oxygen species (ROS). We further showed that the PVC secretome significantly reduces inflammatory responses and endoplasmic reticulum stress in peritoneal macrophages in a mouse model of monosodium urate-induced peritonitis. A cytokine antibody array analysis revealed that the PVC secretome contains high levels of serpin E1 and angiogenin, which may be responsible for the inhibitory effects on mitochondrial ROS generation as well as on inflammasome activation.CONCLUSIONS: Our results suggest that PVCs may be therapeutically useful for the treatment of macrophage- and inflammation-mediated diseases by paracrine action via the secretion of various biological factors.
