[Effects of all-trans retinoic acid on the macrophage function of prostatic stromal cells]

To investigate the effects of all-trans retinoic acid (ATRA) on prostatic stromal cells during wound repair after prostatectomy in vitro.

Each of the M1 and M2 types of monocytic macrophage (THP-1) cells were divided into an experimental, a control and a non-activated group, the M1 macrophages of the former two groups activated by PMA and IFNγ, and the M2 macrophages by PMA and IL-4, respectively. The cells in the two experimental groups were treated with all-trans retinoic acid (ATRA) at 100 nmol/L, followed by detection of the expressions of IL-10, IL-12, IL-6, TNF-α and TGF-β in the supernatant by ELISA. The supernatant was co-cultured with primarily cultured prostatic stromal cells or vascular endothelial cells in different groups. The expressions of RARα, RARβ, RARγ, Arg1, Mmp9 and Soat1 in the macrophages were determined by PCR. The influence of the macrophages on the function of the stromal cells was analyzed by gel shrinkage test, scratch test and vascular endothelial cell tubular vascular formation test. The expression levels of Arg1 mRNA were reexamined under the action of RAR receptor subtype inhibitors.

Compared with the control, the M2 macrophages treated with ATRA showed dramatically up-regulated expressions of IL-10 (［213.38 ± 2.02］ vs ［298.22 ± 1.70］ pg/ml, P < 0.01) and TGF-β (［185.37 ± 1.33］ vs ［246.00 ± 2.14］ pg/ml, P < 0.01). The ATRA-treated macrophage supernatant enhanced the contraction and migration of the prostatic stromal cells and tubular formation of the vascular endothelial cells. The mRNA levels of Arg1 and RARβ were significantly increased in the experimental group, and RARβ was further confirmed to be the key receptor subtype in this process.

ATRA activates prostatic stromal cells and enhances their migration and angiogenesis by acting on macrophages via RARβ.