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.
| Language | English |
|---|---|
| Article number | 72 |
| Number of pages | 21 |
| Journal | Vaccines |
| Volume | 6 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 13 Oct 2018 |
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Keywords
- adjuvant vaccine
- LPS stimulation
- macrophages
- melittin
- PMA differentiated
- pro- and anti-inflammatory cytokines
- THP-1 cells
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Effect of melittin on metabolomic profile and cytokine production in PMA-differentiated THP-1 cells. / Alqarni, Abdulmalik M.; Ferro, Valerie A.; Parkinson, John A.; Dufton, Mark J.; Watson, David G.
In: Vaccines, Vol. 6, No. 4, 72, 13.10.2018.Research output: Contribution to journal › Article
TY - JOUR
T1 - Effect of melittin on metabolomic profile and cytokine production in PMA-differentiated THP-1 cells
AU - Alqarni, Abdulmalik M.
AU - Ferro, Valerie A.
AU - Parkinson, John A.
AU - Dufton, Mark J.
AU - Watson, David G.
PY - 2018/10/13
Y1 - 2018/10/13
N2 - 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.
AB - 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.
KW - adjuvant vaccine
KW - LPS stimulation
KW - macrophages
KW - melittin
KW - PMA differentiated
KW - pro- and anti-inflammatory cytokines
KW - THP-1 cells
UR - http://www.scopus.com/inward/record.url?scp=85055849613&partnerID=8YFLogxK
UR - https://www.mdpi.com/journal/vaccines
U2 - 10.3390/vaccines6040072
DO - 10.3390/vaccines6040072
M3 - Article
VL - 6
JO - Vaccines
T2 - Vaccines
JF - Vaccines
SN - 2076-393X
IS - 4
M1 - 72
ER -