Furthermore, hCAP18/LL-37 Olaparib order is completely absent from the plasma and saliva of these patients; consequently, these patients present chronic periodontitis and overgrowth of Actinobacillus actinomycetemcomitans. Surprisingly, hCAP18/LL-37 has been reported to have antimicrobial activity against A. actinomycetemcomitans, supporting the hypothesis that the deficiency of its peptide may result in periodontitis. In

addition, despite normalized absolute neutrophil count levels, G-CSF-treated SCN patients still often have periodontitis [117] and [118]. According to the maturation cycle of neutrophils, defensins are predominantly detected at the promyelocyte stage, when primary granules mature. In contrast to hCAP18/LL-37, which is primarily detected at the myelocyte stage, when secondary granules mature [119]. Recently, HAX1 gene mutations in SCN patients that result in increased apoptosis in myeloid cells have been identified. The HAX1 gene encodes the hematopoietic cell-specific protein 1 (HS1)-associate protein X-1 (HAX-1), which has been regulated in apoptosis [120]. Thus, deficiency of hCAP18/LL-37 may be associated with maturation arrest in myelopoiesis. Similarly, severe periodontitis is found

in the Papillon–Lefèvre syndrome (PLS), an inheritable disease caused by loss-of-function MEK inhibitor mutations in the cathepsin C gene. Cathepsin C is the activator of serine proteinases, elastase, cathepsin G, and proteinase 3. These patients have been recently found to lack active neutrophil-derived serine proteases. The neutrophils of PLS patients release reduced levels of mature hCAP18/LL-37 because serine proteinases are needed to convert the neutrophil-derived hCAP18/LL-37 into the

mature peptide that possesses antimicrobial activity [121]. These studies suggest that Methane monooxygenase hCAP18/LL-37 plays an important role in innate immunity against periodontal pathogens. In keratinized epithelial cells, hCAP18/LL-37 is inducible with inflammatory disorders, psoriasis, and nickel allergy [50]. Under inflammatory conditions, the epidermis showed abundant immunohistochemical staining of its peptide, while the healthy dermis did not show the presence of the peptide. In non-keratinized epithelial cells, under conditions of dysplasia and inflammatory cervix of the uterus, the strongest expression of hCAP18/LL-37 was detected at both the mRNA and protein levels in the upper spinous and granular layers toward the surface [49]. In fact, we found that the oral lichen planus (OLP) expresses more intense immunohistochemical staining for the hCAP18/LL-37 peptide than the normal epithelium (Fig. 2, unpublished data). Similarly, OLP showed intense immunohistochemical staining of β-defensin-2 (hBD-2) [122]. This increased expression is not related to microbial infection. For example, hCAP18/LL-37 mRNA and its peptide are rapidly expressed in the skin at the site of injury.