Vitamin D3 promotes osteogenic differentiation but also downregulates inflammation promoter-induced IL-6 cytokine and CXCL1 chemokine expression in human PDL cells, suggesting that vitamin D3 both stimulates bone regeneration and antagonizes inflammation in human periodontal tissue.

The steroid hormone metabolite of vitamin D 3 , 1α,25-dihydroxyvitamin D 3 (1,25D3), promotes osteogenic activity and regulates calcium and phosphate metabolism, which are actions regarded as classical vitamin D-regulated functions. Besides its role in these processes, 1,25D3 also seems implicated in the host defense against microbial/proinflammatory attacks. Low serum levels of vitamin D 3 (vitamin D deficiency) are associated with osteoporosis and increased risk of fractures but also inflammatory diseases and their disease progression, presumably via mechanisms associated with 1,25D3-evoked modulation of the innate immune system. 1,25D3 has been reported to modulate many inflammatory responses, suggesting that it regulates multiple transcriptional targets within the inflammatory system. Experimental studies in various experimental systems show that 1,25D3 differentially regulates the production of pro-inflammatory cytokines and chemokines depending on cell type. Importantly, many reports show that 1,25D3 up-regulates expression of the human antimicrobial peptide hCAP-18/LL-37 gene. The hCAP-18/LL-37 gene seems indeed to be an important transcriptional target for 1,25D3. However, only weak evidence is presented showing that 1,25D3 consistently increases the amount of biologically active LL-37 peptide.In the present review, we discuss 1,25D3-induced down-regulation of cytokine/chemokine production and stimulation of hCAP-18/LL-37 gene expression which represent two very important pathways for 1,25D3-evoked regulation of the innate immune response.

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A comparative study on the bis(functionalization) of the Tröger's base core by aromatic and heteroaromatic groups using palladium-catalyzed cross-coupling reactions is presented. Three different reactions, the Suzuki, Stille, and Negishi couplings, were investigated using Tröger's base analogues equally substituted in the 2,8-positions with (HO) 2 B, Bu 3 Sn and ZnCl groups, respectively, as the metallated component. Six aryl halides with different electronic and steric properties were employed as coupling partners. The presence of the bulky and electron-rich phosphane P(tBu) 3 as cocatalyst was found to play an important role. In addition, the

The human antimicrobial peptide cathelicidin LL-37 has, besides its antimicrobial properties, also been shown to regulate apoptosis in a cell type-specific manner. Mechanisms involved in LL-37-regulated apoptotic signaling are not identified. Here, we show that LL-37 reduces the human osteoblast-like MG63 cell number and cell viability in the micromolar concentration range with an IC₅₀ value of about 5 µM. Treatment with 4 µM LL-37 increased the number of annexin V-positive cells and stimulated activation of caspase 3 showing that LL-37 promotes apoptosis. Treatment with 4 µM LL-37 caused an acute and sustained rise in intracellular Ca²⁺ concentration assessed by laser-scanning confocal microscopy of Fluo-4-AM-loaded MG63 cells. LL-37 increased Ca²⁺ also in the presence of the respective L- and T-type voltage-sensitive Ca²⁺ channel blockers nifedipine and NiCl₂. LL-37 had no effect on Ca²⁺ in cells incubated with Ca²⁺-free solution. LL-37 (4 and 8 µM) reduced the MG63 cell number both in the presence and absence of Ca²⁺ in the medium. In conclusion, LL-37 reduces the osteoblast cell number by promoting apoptosis, and furthermore, LL-37 stimulates Ca²⁺ inflow via a mechanism independent of voltage-sensitive Ca²⁺ channels. Interestingly, LL-37-induced lowering of the cell number seems to be mediated via a mechanism independent of Ca²⁺.