Neutrophil Immunomodulatory Activity of Natural Organosulfur Compounds

dc.contributor.authorSchepetkin, Igor A.
dc.contributor.authorKirpotina, Liliya N.
dc.contributor.authorKhlebnikov, Andrie I.
dc.contributor.authorBalasubramanian, Ganesh
dc.contributor.authorQuinn, Mark T.
dc.date.accessioned2020-01-21T20:20:21Z
dc.date.available2020-01-21T20:20:21Z
dc.date.issued2019-05-19
dc.description.abstractOrganosulfur compounds are bioactive components of garlic essential oil (EO), mustard oil, Ferula EOs, asafoetida, and other plant and food extracts. Traditionally, garlic (Allium sativum) is used to boost the immune system; however, the mechanisms involved in the putative immunomodulatory effects of garlic are unknown. We investigated the effects of garlic EO and 22 organosulfur compounds on human neutrophil responses. Garlic EO, allyl propyl disulfide, dipropyl disulfide, diallyl disulfide, and allyl isothiocyanate (AITC) directly activated Ca2+ flux in neutrophils, with the most potent being AITC. Although 1,3-dithiane did not activate neutrophil Ca2+ flux, this minor constituent of garlic EO stimulated neutrophil reactive oxygen species (ROS) production. In contrast, a close analog (1,4-dithiane) was unable to activate neutrophil ROS production. Although 1,3-dithiane-1-oxide also stimulated neutrophil ROS production, only traces of this oxidation product were generated after a 5 h treatment of HL60 cells with 1,3-dithiane. Evaluation of several phosphatidylinositol-3 kinase (PI3K) inhibitors with different subtype specificities (A-66, TGX 221, AS605240, and PI 3065) showed that the PI3K p110δ inhibitor PI 3065 was the most potent inhibitor of 1,3-dithiane-induced neutrophil ROS production. Furthermore, 1,3-dithiane enhanced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), glycogen synthase kinase 3 α/β (GSK-3α/β), and cAMP response element binding (CREB) protein in differentiated neutrophil-like HL60 cells. Density functional theory (DFT) calculations confirmed the reactivity of 1,3-dithiane vs. 1,4-dithiane, based on the frontier molecular orbital analysis. Our results demonstrate that certain organosulfur compounds can activate neutrophil functional activity and may serve as biological response modifiers by augmenting phagocyte functions.en_US
dc.identifier.citationSchepetkin, Igor A, Liliya N Kirpotina, Andrei, I Khlebnikov, Ganesh Balasubramanian, and Mark T. Quinn. "Neutrophil Immunomodulatory Activity of Natural Organosulfur Compounds." Molecules 24, no. 9(May 2019):1809. DOI:10.3390/molecules24091809.en_US
dc.identifier.issn1420-3049
dc.identifier.urihttps://scholarworks.montana.edu/handle/1/15815
dc.language.isoen_USen_US
dc.rightsCC BY: This license lets you distribute, remix, tweak, and build upon this work, even commercially, as long as you credit the original creator for this work. This is the most accommodating of licenses offered. Recommended for maximum dissemination and use of licensed materials.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/legalcodeen_US
dc.titleNeutrophil Immunomodulatory Activity of Natural Organosulfur Compoundsen_US
dc.typeArticleen_US
mus.citation.extentfirstpage1722en_US
mus.citation.extentlastpage1722en_US
mus.citation.issue9en_US
mus.citation.journaltitleMoleculesen_US
mus.citation.volume24en_US
mus.data.thumbpage1en_US
mus.identifier.doi10.3390/molecules24091809en_US
mus.relation.collegeCollege of Letters & Scienceen_US
mus.relation.departmentMicrobiology & Immunology.en_US
mus.relation.universityMontana State University - Bozemanen_US

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