The growth factors important in wound healing, such as insulin-like growth factor I (IGF-I) and transforming

growth factor-α (TGF-α), induce the expression of hCAP18/LL-37 and β-defensin-3 (hBD-3), respectively, in human keratinocytes [123]. In Galunisertib price addition, IGF-I and TGF-α expression is increased in the psoriatic epidermis and during wound healing [124], [125], [126] and [127]. The generation of these growth factors in inflamed lesions without microbial infection may have contributed to this response. In contrast, in cases of inflammatory disease, atopic dermatitis shows significantly lower expression of hCAP18/LL-37 and hBD-2 than psoriasis [128]. Similarly, hCAP18/LL-37 expression has been shown to decrease in the chronic ulcer epithelium [129]. Decreased expression of these peptides can explain the increased susceptibility

to microbial colonization and infection. PF-01367338 concentration Consequently, the level of hCAP18/LL-37 expression may be related to the causes of a disease. For instance, at low concentrations of hCAP18/LL-37 found in normal human epithelia, its peptide could function as an immune watchdog and in cases of high concentrations, when hCAP18/LL-37 is induced by bacteria, bacterial products, or inflammatory cytokines, its peptide could function to promote the migration of immune cells to help control the infection. Alterations in hBD expression in oral squamous cell carcinoma (SCC) have been shown. The expression levels of hBD-1 and hBD-2 varied among cell lines derived from human oral SCC. Although high hBD-2 mRNA expression is detected in all cell lines examined, some of

the cell lines did not show hBD-1 mRNA expression [130]. In addition, hBD-1 and hBD-2 mRNA expression was significantly lower in oral SCC as compared to the normal oral epithelium [131]. An immunohistochemical ADAMTS5 study indicated that well-differentiated SCCs showed strong immunoreactivity for hBD-2 around keratin pearls, whereas no immunoreactivity was observed in poorly differentiated SCCs. Keratin pearl formation with SCC tends to induce a more intense expression of hBD-2 at both peptide and mRNA levels. In contrast, hBD-2 peptide and its mRNA are undetected in poorly differentiated SCCs [132]. Similar results are obtained in cervical cancer [133]. In general, poorly differentiated SCCs have a more aggressive course and worse prognosis than well-differentiated SCCs. These results suggest that hBD deficiency leads to the formation of microbial colonies, which in turn induces inflammation and promotes tumor progression. We have demonstrated that the expression of hCAP18/LL-37 mRNA is undetected in 16 cell lines from human oral SCC (data unpublished). A similar result is obtained in that hCAP18/LL-37 peptide expression is decreased in colonic epithelial cancer cells than in the normal colonic tissue.