The Protective Effects of Melittin on Propionibacterium acnes–Induced Inflammatory Responses In Vitro and In Vivo

• Published in: Journal of investigative dermatology Vol. 134; no. 7; pp. 1922 - 1930
• Main Authors: Lee, Woo-Ram, Kim, Kyung-Hyun, An, Hyun-Jin, Kim, Jung-yeon, Chang, Young-Chae, Chung, Hyun, Park, Yoon-Yub, Lee, Myeong-Lyeol, Park, Kwan-kyu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2014; Elsevier Limited
• Subjects: Animals; Anti-Inflammatory Agents - immunology; Anti-Inflammatory Agents - pharmacology; Apis mellifera; Cell Line; Disease Models, Animal; Gene Expression - drug effects; Gene Expression - immunology; Gram-Positive Bacterial Infections - drug therapy; Gram-Positive Bacterial Infections - immunology; Humans; Interleukin-1beta - genetics; Keratinocytes - cytology; Keratinocytes - immunology; Keratinocytes - microbiology; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - immunology; Melitten - immunology; Melitten - pharmacology; Mice; Mice, Inbred ICR; NF-kappa B - metabolism; Propionibacterium; Propionibacterium acnes - drug effects; Toll-Like Receptor 2 - immunology; Toll-Like Receptor 2 - metabolism; Tumor Necrosis Factor-alpha - genetics
• ISSN: 0022-202X; 1523-1747; 1523-1747
• DOI: 10.1038/jid.2014.75

Melittin is the main component in the venom of the honey bee (Apis mellifera). It has multiple effects including antibacterial, antiviral, and anti-inflammatory activities in various cell types. However, the anti-inflammatory mechanisms of melittin have not been elucidated in Propionibactierium acnes (P. acnes)–induced keratinocyte or inflammatory skin disease animal models. In this study, we examined the effects of melittin on the production of inflammatory cytokines in heat-killed P. acnes–induced HaCaT cells. Heat-killed P. acnes–treated keratinocytes increased the expression of pro-inflammatory cytokines and Toll-like receptor 2. However, melittin treatment significantly suppressed the expression of these cytokines through regulation of the NF-κB and MAPK signaling pathways. Subsequently, the living P. acnes (1 × 107 CFU) were intradermally injected into the ear of mice. Living P. acnes–injected ears showed cutaneous erythema, swelling, and granulomatous response at 24 hours after injection. However, melittin-treated ears showed markedly reduced swelling and granulomatous responses compared with ears injected with only living P. acnes. These results demonstrate the feasibility of applying melittin for the prevention of inflammatory skin diseases induced by P. acnes.