PMID- 21593770 OWN - NLM STAT- MEDLINE DCOM- 20111003 LR - 20131121 IS - 1523-1747 (Electronic) IS - 0022-202X (Linking) VI - 131 IP - 8 DP - 2011 Aug TI - Antimicrobial and anti-inflammatory effects of Cecropin A(1-8)-Magainin2(1-12) hybrid peptide analog p5 against Malassezia furfur infection in human keratinocytes. PG - 1677-83 LID - 10.1038/jid.2011.112 [doi] AB - The lipophilic fungus Malassezia furfur (M. furfur) is a commensal microbe associated with several chronic diseases such as pityriasis versicolor, folliculitis, and seborrheic dermatitis. Because M. furfur-related diseases are difficult to treat and require prolonged use of medications, the treatment for M. furfur-related skin diseases is supposed to gain control over M. furfur growth and the inflammation associated with it, as well as to prevent secondary infections. In this study, we investigated the antifungal and anti-inflammatory effects of cecropin A(1-8)-magainin 2(1-12) hybrid peptide analog P5 on M. furfur. The minimal inhibitory concentration of P5 against M. furfur was 0.39 muM, making it 3-4 times more potent than commonly used antifungal agents such as ketoconazole (1.5 muM) or itraconazole (1.14 muM). P5 efficiently inhibited the expression of IL-8 and Toll-like receptor 2 in M. furfur-infected human keratinocytes without eukaryotic cytotoxicity at its fungicidal concentration. Moreover, P5 significantly downregulated NF-kappaB activation and intracellular calcium fluctuation, which are closely related with enhanced responses of keratinocyte inflammation induced by M. furfur infection. Taken together, these observations suggest P5 may be a potential therapeutic agent for M. furfur-associated human skin diseases because of its distinct antifungal and anti-inflammatory action. FAU - Ryu, Sunhyo AU - Ryu S AD - Department of Dermatology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. FAU - Choi, Soon-Yong AU - Choi SY FAU - Acharya, Samudra AU - Acharya S FAU - Chun, Young-Jin AU - Chun YJ FAU - Gurley, Catherine AU - Gurley C FAU - Park, Yoonkyung AU - Park Y FAU - Armstrong, Cheryl A AU - Armstrong CA FAU - Song, Peter I AU - Song PI FAU - Kim, Beom-Joon AU - Kim BJ LA - eng PT - Journal Article DEP - 20110519 PL - United States TA - J Invest Dermatol JT - The Journal of investigative dermatology JID - 0426720 RN - 0 (Antifungal Agents) RN - 0 (Antimicrobial Cationic Peptides) RN - 0 (Interleukin-8) RN - 0 (NF-kappa B) RN - 0 (cecropin A(1-8)magainin 2(1-12)) RN - SY7Q814VUP (Calcium) SB - IM MH - Antifungal Agents/*pharmacology MH - Antimicrobial Cationic Peptides/*pharmacology MH - Calcium/metabolism MH - Calcium Signaling/drug effects/immunology MH - Cell Nucleus/immunology/metabolism MH - Cells, Cultured MH - Dermatomycoses/*drug therapy/immunology MH - Dose-Response Relationship, Drug MH - Humans MH - Interleukin-8/metabolism MH - Keratinocytes/cytology/immunology/*microbiology MH - Malassezia/*drug effects/immunology MH - Microbial Sensitivity Tests MH - NF-kappa B/metabolism EDAT- 2011/05/20 06:00 MHDA- 2011/10/04 06:00 CRDT- 2011/05/20 06:00 PHST- 2011/05/20 06:00 [entrez] PHST- 2011/05/20 06:00 [pubmed] PHST- 2011/10/04 06:00 [medline] AID - S0022-202X(15)35362-8 [pii] AID - 10.1038/jid.2011.112 [doi] PST - ppublish SO - J Invest Dermatol. 2011 Aug;131(8):1677-83. doi: 10.1038/jid.2011.112. Epub 2011 May 19.