Skip to main content
. Author manuscript; available in PMC: 2011 Jun 10.
Published in final edited form as: Mol Cell Endocrinol. 2010 Feb 13;321(2):103–111. doi: 10.1016/j.mce.2010.02.013

Figure 3. Vitamin D and the feedback regulation of monocyte/macrophage production of hCAP.

Figure 3

Intracrine induction of monocyte/macrophage hCAP production by vitamin D is promoted following TLR2/1 pathogen-sensing. This mechanism involves TLR2/1 induction of interleukin-15 (IL-15), a potent stimulator of 1α-hydroxylase (1α) expression and activity. As a counterpoint, intracrine generated 1,25(OH)2D acts to suppress TLR2 expression thereby desensitizing monocytes/macrophages to further TLR2/1 activation. Locally generated 1,25(OH)2D also stimulates expression of the enzyme 24-hydroxylase (24) which catalyzes the conversion of 25OHD and/or 1,25(OH)2D to less active metabolites such as 1,24,25-trihydroxyvitamin D (1,24,25(OH)3D). Monocytes/macrophages also express a truncated splice variant (SV) form of the 24-hydroxylase protein which lacks the required mitochondrial-targeting sequence and is therefore functionally inactive and located in the cytosol. Despite this the SV protein retains its steroid-binding pocket and can thus act as a decoy for 25OHD or 1,25(OH)2D.