Anti-inflammatory effect of collagen tripeptide in atopic dermatitis

Background: Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease in which type 2 allergic inflammation plays an important role. Collagen tripeptide (CTP) is a functional collagen fraction with a high content of Gly-X-Y tripeptides. Objective: To examine the effect of CTP on inflammation in AD. Methods: Levels of inflammatory cytokines and chemokines, such as thymus-and activation-regulated chemokine (TARC), macrophage-derived chemokine, and thymic stromal lymphopoietin (TSLP), were examined in human keratinocytes supplemented with or without CTP under AD-like inflammation. To evaluate the functional effect of CTP, a migration assay was performed using the supernatants of cultured keratinocytes treated with CTP. The signaling pathway for CTP inhibitory activity was also determined. Additionally, we conducted a clinical trial with seventeen AD patients who were assigned randomly to receive daily for 12 weeks either 3.9 g of a CTP product or normal collagen peptides (CP). The eruption area, severity scoring of atopic dermatitis (SCORAD), skin hydration, transepidermal water loss (TEWL), and itching score were evaluated. The levels of TARC, serum IgE, lactate dehydrogenase, and eosinophil counts at week 12 were also compared with those at the start of administration. Results: In human keratinocytes, TARC and TSLP mRNA and protein levels were inhibited significantly by CTP treatment under AD-like inflammation. Supernatants obtained from CTP-treated keratinocytes inhibited cell migration. STAT1 phosphorylation was significantly decreased by CTP in a dose-dependent manner. In the clinical trial, 13 patients (7 for CTP, 6 for CP) completed the study. The eruption area, SCORAD, and TEWL at week 12 were reduced significantly compared with the initial values in the CTP but not CP group. A significant reduction in the serum TARC level was observed only in the CTP group at week 12. Other blood parameters were not improved in either group. Conclusion: CTP may have therapeutic benefit for AD by inhibiting type 2-skewed allergic inflammation. (C) 2017 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.