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Vaccines 2018, 6(4), 72; https://doi.org/10.3390/vaccines6040072

Effect of Melittin on Metabolomic Profile and Cytokine Production in PMA-Differentiated THP-1 Cells

1
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK
2
WestCHEM Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, UK
*
Author to whom correspondence should be addressed.
Received: 11 September 2018 / Revised: 9 October 2018 / Accepted: 11 October 2018 / Published: 13 October 2018
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Abstract

Melittin, the major active peptide of honeybee venom (BV), has potential for use in adjuvant immunotherapy. The immune system response to different stimuli depends on the secretion of different metabolites from macrophages. One potent stimulus is lipopolysaccharide (LPS), a component isolated from gram-negative bacteria, which induces the secretion of pro-inflammatory cytokines in macrophage cell cultures. This secretion is amplified when LPS is combined with melittin. In the present study, pure melittin was isolated from whole BV by flash chromatography to obtain pure melittin. The ability of melittin to enhance the release of tumour necrosis factor-α (TNF-α), Interleukin (IL-1β, IL-6, and IL-10) cytokines from a macrophage cell line (THP-1) was then assessed. The response to melittin and LPS, applied alone or in combination, was characterised by metabolic profiling, and the metabolomics results were used to evaluate the potential of melittin as an immune adjuvant therapy. The addition of melittin enhanced the release of inflammatory cytokines induced by LPS. Effective chromatographic separation of metabolites was obtained by liquid chromatography-mass spectrometry (LC-MS) using a ZIC-pHILIC column and an ACE C4 column. The levels of 108 polar and non-polar metabolites were significantly changed (p ˂ 0.05) following cell activation by the combination of LPS and melittin when compared to untreated control cells. Overall, the findings of this study suggested that melittin might have a potential application as a vaccine adjuvant. View Full-Text
Keywords: melittin; pro- and anti-inflammatory cytokines; LPS stimulation; THP-1 cells; PMA differentiated; macrophages; adjuvant vaccine melittin; pro- and anti-inflammatory cytokines; LPS stimulation; THP-1 cells; PMA differentiated; macrophages; adjuvant vaccine
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Alqarni, A.M.; Ferro, V.A.; Parkinson, J.A.; Dufton, M.J.; Watson, D.G. Effect of Melittin on Metabolomic Profile and Cytokine Production in PMA-Differentiated THP-1 Cells. Vaccines 2018, 6, 72.

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