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Effect of Bee Venom and Its Fractions on the Release of Pro-Inflammatory Cytokines in PMA-Differentiated U937 Cells Co-Stimulated with LPS

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Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK
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WestCHEM Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, UK
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#204, Beesen Co. Ltd., Bio Venture Town, Yuseong Daero 1662, 34054 Dae Jeon, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Diane M. Harper
Vaccines 2016, 4(2), 11; https://doi.org/10.3390/vaccines4020011
Received: 2 March 2016 / Revised: 12 April 2016 / Accepted: 13 April 2016 / Published: 19 April 2016
The venom of Apis mellifera (honey bee) has been reported to play a role in immunotherapy, but existing evidence to support its immuno-modulatory claims is insufficient. Four fractions from whole bee venom (BV) were separated using medium pressure liquid chromatography. Their ability to induce the production of cytokines TNFα, IL-1β and IL-6 in phorbol-12-myristate-13-acetate (PMA)-treated U937 cells was assessed. The levels of the three cytokines produced by stimulation with the four fractions and crude BV without LPS were not significantly different from negative control values. However, co-stimulation of the cells with LPS and Fraction 4 (F-4) induced a 1.6-fold increase in TNF-α level (p < 0.05) compared to LPS alone. Likewise, LPS-induced IL-1β production was significantly synergised in the presence of F-1 (nine-fold), F-2 (six-fold), F-3 (four-fold) and F-4 (two-fold) fractions, but was only slightly enhanced with crude BV (1.5-fold) relative to LPS. Furthermore, the LPS-stimulated production of IL-6 was not significantly increased in cells co-treated with F-2 and F-3, but the organic fraction (F-4) showed an inhibitory effect (p < 0.05) on IL-6 production. The latter was elucidated by NMR spectroscopy and found to contain(Z)-9-eicosen-1-ol. The effects observed with the purified BV fractions were more marked than those obtained with the crude sample. View Full-Text
Keywords: bee venom; pro-inflammatory cytokines; LPS stimulation; U937 cells; PMA differentiated; ELISA; (Z)-9-eicosen-1-ol; Apis mellifera bee venom; pro-inflammatory cytokines; LPS stimulation; U937 cells; PMA differentiated; ELISA; (Z)-9-eicosen-1-ol; Apis mellifera
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Tusiimire, J.; Wallace, J.; Woods, N.; Dufton, M.J.; Parkinson, J.A.; Abbott, G.; Clements, C.J.; Young, L.; Park, J.K.; Jeon, J.W.; Ferro, V.A.; Watson, D.G. Effect of Bee Venom and Its Fractions on the Release of Pro-Inflammatory Cytokines in PMA-Differentiated U937 Cells Co-Stimulated with LPS. Vaccines 2016, 4, 11.

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