Journal
ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS
Volume 65, Issue 1, Pages 69-81Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00005-016-0411-0
Keywords
Retinoic acid receptor; Hematopoiesis; Neutrophils; Monocytes; All-trans retinoic acid; Agonist; Antagonist
Categories
Funding
- European Union's Seventh Framework Programme for research, technological development, and demonstration [315902]
- Marie Curie Research Fellowship
- National Science Centre in Poland [2013/11/N/NZ3/00197]
Ask authors/readers for more resources
Activities of the retinoic acid receptor (RAR)alpha and RAR gamma are important to hematopoiesis. Here, we have investigated the effects of receptor selective agonists and antagonists on the primitive human hematopoietic cell lines KG1 and NB-4 and purified normal human hematopoietic stem cells (HSCs). Agonizing RAR alpha (by AGN195183) was effective in driving neutrophil differentiation of NB-4 cells and this agonist synergized with a low amount (10 nM) of 1 alpha, 25-dihydroxyvitamin D-3 to drive monocyte differentiation of NB-4 and KG1 cells. Treatment of cultures of human HSCs (supplemented with stem cell factor +/- interleukin 3) with an antagonist of all RARs (AGN194310) or of RAR alpha (AGN196996) prolonged the lifespan of cultures, up to 55 days, and increased the production of neutrophils and monocytes. Slowing down of cell differentiation was not observed, and instead, hematopoietic stem and progenitor cells had expanded in number. Antagonism of RAR gamma (by AGN205728) did not affect cultures of HSCs. Studies of CV-1 and LNCaP cells transfected with RAR expression vectors and a reporter vector revealed that RAR gamma and RAR beta are activated by sub-nM all-trans retinoic acid (EC50-0.3 nM): similar to 50-fold more is required for activation of RARa (EC50-16 nM). These findings further support the notion that the balance of expression and activity of RAR alpha and RAR gamma are important to hematopoietic stem and progenitor cell expansion and differentiation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available