Interestingly, pDCs are also found in Vemurafenib oral lichen planus (OLP) and in periodontitis [111] and [112]. In particular, significant recruitment of pDCs producing IFN-α within

the lichenoid inflammatory infiltrate and close cell–cell contacts between pDCs and mature dendritic cells (DCs) have been demonstrated. These data indicate that recruitment of different subtypes of DC, including pDCs, may play a pivotal role in the development of the lichenoid inflammatory infiltrate that typically occurs in OLP. We hypothesize that by analogy with the hCAP18/LL-37 and self-DNA complexes that activate pDCs in psoriasis, its peptide increases in OLP. Binding of self-DNA released from damaged or apoptotic cells to hCAP18/LL-37 may be potentially developed as therapies for OLP and other chronic inflammatory diseases. Additionally, hCAP18/LL-37 induced angiogenesis, and its peptide resulted in neovascularization both www.selleckchem.com/products/PD-0325901.html in the chorioallantoic membrane assay and in a rabbit hind-limb ischemia [113]. This peptide directly activated endothelial cells to proliferate and form vessel-like structures in human endothelial cells, HUVECs, and shown to cause endothelial sprouting from hamster aortic rings.

The angiogenic activity of hCAP18/LL-37 appears to be mediated by the interaction of peptide with FPRL-1 in endothelial cells. It has been demonstrated that human β-defensin-3 (hBD-3), hCAP18/LL-37, and α-defensins are present in the μg/ml range in children’s saliva. The concentration of α-defensins was significantly higher in children with no caries than in those with caries, whereas the concentration of hCAP18/LL-37 and

hBD-3 did not correlate with caries [114]. In contrast, the expression of hCAP18/LL-37 was upregulated in the inflamed Interleukin-2 receptor gingival tissue in comparison with healthy gingival tissue and was correlated positively with the depth of the gingival crevice [115], indicating that hCAP18/LL-37 expression in the gingival tissue is associated with the severity of periodontal disease. In addition, there are variations in the responses of oral epithelial cells to different bacteria and in the sensitivity of oral flora to the peptides [116]. For example, Prevotella intermedia induced the expression of hCAP-18/LL-37 and hBD-1, hBD-2, and hBD-3; Fusobacterium nucleatum, hBD-2 and hBD-3; and Porphyromonas gingivalis, hBD-2. Other species associated with periodontal disease, such as Tannerella forsythia and Treponema denticola, either did not induce expression or caused a down-regulation of steady state mRNA levels. Expression of hCAP18/LL-37 in the gingival epithelial cells was similar; P. gingivalis did not induce expression, whereas A. actinomycetemcomitans, F. nucleatum, P. intermedia, and E. corrodens upregulated the expression of hCAP18/LL-37 [115].