Expression of CYP2R1 and VDR in human brain pericytes: the neurovascular vitamin D autocrine/paracrine model.

International audience: 1,25 dihydroxyvitamin D3 (1,25D) is a hormone produced from vitamin D through two hydroxylating steps catalyzed successively in the liver by the vitamin D 25 hydroxylase Cyp2R1, and in the kidney by the 25-hydroxyvitamin D3 1-hydroxylase Cyp27B1. 1,25D behaves like a steroid hormone. It regulates gene transcription by interacting with a nuclear receptor named VDR for vitamin D receptor. Although the role of vitamin D is historically related to rickets, its physiological function largely encompasses bone tissues. Accumulating evidence leads to consider 1,25D also as a neurosteroid. For example, both VDR and CYP27B1 are expressed in brain cells. Likewise the neuroprotective and anti-inflammatory potential of 1,25D in nervous tissue is experimentally demonstrated. The regulation of Cyp27B1, which catalyzes the last step of 1,25D synthesis, by the inflammatory cytokines TNF- and INF- has been recently reported. However, the fate of Cyp2R1 which catalyzes the first enzymatic reaction of the vitamin D metabolism has retained no attention. Using human brain pericytes we studied the expression of CYP2R1 and VDR genes when these cells were challenged to an inflammatory stimulus. We showed a significant up-regulation of these two genes in human brain pericytes challenged with TNF- and INF-. These results suggest the existence of an autocrine/paracrine vitamin D system in the neurovascular unit. The function of this novel signaling system might be critical in the control of neuro-inflammation and in brain pathologies