Int J Stem Cells.  2019 Nov;12(3):419-429. 10.15283/ijsc19115.

Perivascular Stem Cells Suppress Inflammasome Activation during Inflammatory Responses in Macrophages

Affiliations
  • 1Department of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon, Korea. shhong@kangwon.ac.kr
  • 2Scripps Korea Antibody Institute and Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Korea.
  • 3Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Korea.
  • 4Department of Physiology, School of Medicine, Kangwon National University, Chuncheon, Korea.
  • 5Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kangwon National University, Chuncheon, Korea.

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.

Keyword

Perivascular stem cells; Inflammation; Inflammasome; Macrophage

MeSH Terms

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*
Biological Factors
Inflammasomes
Plasminogen Activator Inhibitor 1
Reactive Oxygen Species
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