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Protective effect of melittin against inflammation and apoptosis on Propionibacterium acnes-induced human THP-1 monocytic cell.

Abstract
Melittin is a cationic, hemolytic peptide that is the main toxic component in the venom of the honey bee (Apis mellifera). It has been used in treatment of various chronic inflammatory diseases. However, the cellular mechanism and the anti-apoptotic effect of melittin in Propionibactierium acnes (P. acnes)-induced THP-1 cells have not been explored. In the present study, we investigated the anti-inflammatory and anti-apoptotic mechanism by examining the effect of melittin on P. acnes-induced THP-1 monocytic cells. THP-1 monocytic cells were stimulated by heat-killed P. acnes in the presence of melittin. The expression levels of pro-inflammatory cytokines, NF-κB signaling, caspase family, and PARP signaling were measured by ELISA or Western blot analysis. The number of apoptotic cells and changes of cell morphology were examined using fluorescence microscopy and flow cytometry. Heat-killed P. acnes increased the secretion of pro-inflammatory cytokines and cleavage of caspase-3 and -8 in heat-killed P. acnes-induced THP-1 cells. However, treatment with melittin inhibited the pro-inflammatory cytokines and cleavage of the caspase-3 and -8. Moreover, the cleaved PARP appeared after 8h of heat-killed P. acnes treatment and its cleavage was reduced by melittin treatment. These results demonstrate that 1.0×10(7) CFU/ml of heat-killed P. acnes induces THP-1 cell apoptosis and secretion of inflammatory cytokines. Also, administration of melittin significantly decreases the expression of various inflammatory cytokines in heat-killed P. acnes-treated THP-1 monocytic cells. In particular, melittin exerts anti-apoptotic effects against 1.0×10(7) CFU/ml of heat-killed P. acnes injury to THP-1 cells.
AuthorsWoo-Ram Lee, Kyung-Hyun Kim, Hyun-Jin An, Jung-Yeon Kim, Sang-Mi Han, Kwang-Gil Lee, Kwan-Kyu Park
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 740 Pg. 218-26 (Oct 05 2014) ISSN: 1879-0712 [Electronic] Netherlands
PMID25062791 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier B.V. All rights reserved.
Chemical References
  • Anti-Inflammatory Agents
  • Interleukin-1beta
  • Interleukin-8
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Melitten
  • CASP8 protein, human
  • Caspase 3
  • Caspase 8
Topics
  • Anti-Inflammatory Agents (pharmacology)
  • Apoptosis (drug effects)
  • Caspase 3 (metabolism)
  • Caspase 8 (metabolism)
  • Cell Line
  • Humans
  • Interleukin-1beta (metabolism)
  • Interleukin-8 (metabolism)
  • Melitten (pharmacology)
  • Monocytes (drug effects, metabolism, microbiology)
  • Propionibacterium acnes
  • Toll-Like Receptor 2 (metabolism)
  • Toll-Like Receptor 4 (metabolism)
  • Tumor Necrosis Factor-alpha (metabolism)

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