<b>Vitamin D</b><b>₃</b><b> analog maxacalcitol (OCT) induces hCAP-18/LL-37 production in human oral epithelial </b><b>cells </b>

Abstract

Maxacalcitol (22-oxacalcitriol: OCT) is a synthetic vitamin D 3 analog with a limited calcemic effect. In this study, we investigated whether OCT increases the production of LL-37/CAP-18, a human cathelicidin antimicrobial peptide, in human gingival/oral epithelial cells. A human gingival epithelial cell line (Ca9-22) and human oral epithelial cell lines (HSC-2, HSC-3, and HSC-4) exhibited the enhanced expression of LL-37 mRNA upon stimulation with OCT as well as active metabolites of vitamins D 3 and D 2 . Among the human epithelial cell lines, Ca9-22 exhibited the strongest response to these vitamin D-related compounds. OCT induced the higher production of CAP-18 (ng/mL order) until 6 days time-dependently in Ca9-22 cells in culture. The periodontal pathogen Porphyromonas gingivalis was killed by treatment with the LL-37 peptide. These findings suggest that OCT induces the production of hCAP-18/LL-37 in a manner similar to that induced by the active metabolite of vitamin D 3 .

Preliminary investigation of the vitamin D pathway in periodontal connective tissue cells

“…In the study by Tada et al., a human gingival epithelial cell line (Ca9‐22) exhibited increased expression of hCAP‐18/LL‐37 upon stimulation with either 100 nM 1,25‐(OH)VD analog or 100 nM 1,25‐(OH)VD. The enhancement was as much as 75‐fold compared with that of the negative control in 24 hours and even higher with longer incubation time.…”

“…hCAP‐18/LL‐37 has also been detected in human gingival crevicular fluids (GCF), with patients with aggressive or chronic periodontitis exhibiting higher LL‐37 levels in GCF than controls . In in vitro studies, stimulation of gingival/oral epithelial cells using 25‐(OH)VD, 1,25‐(OH)VD, or its analog resulted in an elevation of hCAP‐18/LL‐37 expression . The question was raised whether the vitamin D induction of hCAP‐18/LL‐37 may also exist in periodontal soft tissue cells such as hGFs and hPDLCs.…”

<i><b>Porphyromonas gingivalis</b></i><b>-induced IL-33 down-regulates hCAP-18/LL-37 production in human gingival epithelial </b><b>cells </b>

“…We reported previously that P. gingivalis infection increases IL-33 production in human gingival epithelial cells in a gingipain-dependent manner (30). OCT induces the production of hCAP-18 protein, but not LL-37 protein by human gingival epithelial cells (31). We showed that OCT-induced hCAP-18/ LL-37 production was attenuated by the infection with P. gingivalis ATCC 33277, but not a gingipain-null P. gingivalis mutant KDP136.…”

“…1A). We reported previously that Ca9-22 cells produce the precursor hCAP-18, but not LL-37, induced by OCT (31). Then, we examined whether P. gingivalis infection induces hCAP-18 production by Ca9-22 cells.…”

“…Calcitriol, a biologically active metabolite of vitamin D 3 (1α,25-dihydroxyvitamin D 3 ), is an agonist of the vitamin D receptor (VDR) and is essential for maintaining human health (17). We reported recently that maxacalcitol (1α,25-dihydroxy-22-oxavitamin D 3 , 22-oxacalcitriol: OCT), an active synthetic analog of calcitriol, increases hCAP-18/LL-37 production in human gingival/oral epithelial cells (31).…”