Vitamin D-induced up-regulation of human keratinocyte cathelicidin anti-microbial peptide expression involves retinoid X receptor α.
Svensson. Daniel D; Nebel. Daniel D; Voss. Ulrikke U; Ekblad. Eva E; Nilsson. Bengt-Olof BO
Key Findings
- Calcitriol (1,25D3) raises CAMP (LL‑37) mRNA several‑fold and protein levels about 13‑fold in human skin cells.
- The boost in LL‑37 depends on the presence of the RXRα receptor; knocking down RXRα stops the effect.
- Vitamin‑D treatment actually lowers VDR (vitamin‑D receptor) expression while still increasing LL‑37.
Practical Outcomes
- For biohackers, taking vitamin D (especially in its active form) may enhance skin antimicrobial defenses via LL‑37, but the response likely requires adequate RXRα activity. Pairing vitamin D with nutrients that support RXR function (e.g., omega‑3 fatty acids or retinoids) could be more effective than vitamin D alone. However, because the study used calcitriol at relatively high concentrations, standard vitamin D3 supplements may need higher doses or longer periods to achieve similar skin effects, and safety should be monitored.
Summary
The study shows that the active form of vitamin D (calcitriol) can dramatically boost the skin's production of the antimicrobial peptide LL‑37, but it needs a partner protein called RXRα to work. This effect happens without increasing the amount of vitamin‑D receptors themselves.
Abstract
The biologically active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D3), has been reported to positively regulate the human cathelicidin anti-microbial peptide (CAMP) gene coding for LL-37, but the mechanisms are not completely understood. We have determined the expression of CAMP, vitamin D receptor (VDR), and the retinoid X receptor (RXR) isoforms in human skin and gingival tissue biopsies and investigated the signaling pathways involved in 1,25D3-induced upregulation of CAMP. Human skin and gingival biopsies exhibited few VDR-immunoreactive cells within the stratum basale, whereas rat colon enterocytes (positive control) possessed abundant VDR immunoreactivity. Nuclear VDR immunoreactivity was demonstrated in human skin keratinocytes (HaCaT cells). Gene analysis revealed that human skin biopsies expressed higher levels of both CAMP and RXRα mRNA than human gingival biopsies, whereas VDR and RXRβ transcript levels were similar in skin and gingiva. In HaCaT cells, treatment with 1,25D3 (5 nM and 1 μM) for 4 and 24 h up-regulated CAMP mRNA several fold, and treatment with 1,25D3 for 24 h increased protein expression of the pro-form of LL-37 (hCAP-18) by about 13 times. The 1,25D3-evoked stimulation of HaCaT CAMP expression was associated with attenuated VDR mRNA and protein expression. Treatment with RXRα short interfering RNA reversed the 1,25D3-induced CAMP expression in HaCaT cells, showing that RXRα is involved in the up-regulation of CAMP by 1,25D3. We conclude that the 1,25D3-evoked stimulation of CAMP expression in human skin keratinocytes is dependent on RXRα but is not associated with the up-regulation of VDR expression.
Study Information
pubmed
2016
2016-06-30T00:00:00.000Z
10.1007/s00441-016-2449-z
11
38