IL-18/IL-18R1 promotes circulating fibrocyte differentiation in the aging population
- 19 March 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Inflammation Research
- Vol. 69 (5), 497-507
- https://doi.org/10.1007/s00011-020-01330-4
Abstract
Background Fibrosis in multiple organs increases with age. Circulating fibrocytes are bone-marrow-derived mesenchymal progenitors that contribute to heart, lung, and kidney fibrosis under the diseased conditions. Whether circulating fibrocytes contribute to aging-related fibrosis is very limited. Methods and results We measured the proportion and differentiation of circulating fibrocytes (CD45+/CD34+/collagen I+) from elders (n = 12) and adults (n = 12) using flow cytometry. Differentiated fibrocytes in the culture dishes were isolated and microarray was performed. The percentage of circulating fibrocytes in elders (1.95 ± 0.43%) was comparable to that in the adults (1.71 ± 0.38%). Cultured fibrocytes displayed enhanced potential of differentiation in the elder group (67.91 ± 5.88%) vs the adult group (44.03 ± 7.98%). In addition, expression of fibroblast activation markers and cell migratory ability were also increased in differentiated fibrocytes from elders. Microarray analysis revealed that differentiated fibrocytes from elders expressed high level of interleukin-18 (IL-18) receptor 1 (IL-18R1). Furthermore, we found IL-18 was elevated in the plasma of elders and IL-18/IL-18R1 was shown to promote fibrocyte differentiation. Conclusion Circulating fibrocytes from elders had an enhanced capacity to differentiate into myofibroblasts, and might contribute to age-dependent fibrosis. Age-dependent increment of differentiation at least in part arose from their enhanced expression of IL-18R1. Inhibiting fibrocyte differentiation might be useful as an adjuvant treatment to delay the fibrosis process in aging population.Keywords
Funding Information
- Jiangsu University (JLY20180073)
- Scientific Research Project of Education Department of Liaoning Province (LZ2019017, LZ2019021)
This publication has 32 references indexed in Scilit:
- Aging promotes pro-fibrotic matrix production and increases fibrocyte recruitment during acute lung injuryAdvances in Bioscience and Biotechnology, 2014
- Aberrant differentiation of fibroblast progenitors contributes to fibrosis in the aged murine heart: role of elevated circulating insulin levelsThe FASEB Journal, 2012
- Bone Marrow-Derived Cells Contribute to Fibrosis in the Chronically Failing HeartThe American Journal of Pathology, 2010
- Circulating monocytes from systemic sclerosis patients with interstitial lung disease show an enhanced profibrotic phenotypeLaboratory Investigation, 2010
- Resveratrol blocks interleukin-18-EMMPRIN cross-regulation and smooth muscle cell migrationAmerican Journal of Physiology-Heart and Circulatory Physiology, 2009
- Circulating Fibrocytes Are an Indicator of Poor Prognosis in Idiopathic Pulmonary FibrosisAmerican Journal of Respiratory and Critical Care Medicine, 2009
- Increased Circulating Fibrocytes in Asthma with Chronic Airflow ObstructionAmerican Journal of Respiratory and Critical Care Medicine, 2008
- Bone marrow‐derived myofibroblasts contribute functionally to scar formation after myocardial infarctionThe Journal of Pathology, 2008
- Bone marrow-derived fibroblast precursors mediate ischemic cardiomyopathy in miceProceedings of the National Academy of Sciences of the United States of America, 2006
- The origins of age-related proinflammatory stateBlood, 2005