The protective effects of melittin on Propionibacterium acnes-induced inflammatory responses in vitro and in vivo.
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 × 10(7) 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.
Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu, South Korea.
Woo-Ram
WR
Lee
Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu, South Korea.
Kyung-Hyun
KH
Kim
Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu, South Korea.
Hyun-Jin
HJ
An
Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu, South Korea.
Jung-Yeon
JY
Kim
Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu, South Korea.
Young-Chae
YC
Chang
Department of dermatology, College of Medicine, Catholic University of Daegu, Daegu, South Korea.
Hyun
H
Chung
Department of Physiology, College of Medicine, Catholic University of Daegu, Daegu, South Korea.
Yoon-Yub
YY
Park
Department of Agricultural Biology, National Institute of Agricultural Science and Technology, Suwon, South Korea.
Myeong-Lyeol
ML
Lee
Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu, South Korea. Electronic address: kkpark@cu.ac.kr.
Kwan-Kyu
KK
Park
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000494:pharmacology*; D002460:Cell Line; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000276:immunology; D008555:Melitten / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D011425:Propionibacterium acnes / Q000187:drug effects*; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D016328:NF-kappa B; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D008555:Melitten