scholarly journals Innate Immunomodulatory Activity of Cedrol, a Component of Essential Oils Isolated from Juniperus Species

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7644
Author(s):  
Gulmira Özek ◽  
Igor A. Schepetkin ◽  
Moldir Yermagambetova ◽  
Temel Özek ◽  
Liliya N. Kirpotina ◽  
...  
Keyword(s):  
Essential Oils ◽  
Compositional Analysis ◽  
Formyl Peptide Receptor ◽  
Human Neutrophils ◽  
Immunomodulatory Activity ◽  
Neutrophil Chemotaxis ◽  
Pharmacophore Mapping ◽  
Peptide Receptor ◽  
Formyl Peptide ◽  
Similarities And Differences

Little is known about the immunomodulatory activity of essential oils isolated from Juniperus species. Thus, we isolated essential oils from the cones and leaves of eight juniper species found in Montana and in Kazakhstan, including J. horizontalis, J. scopolorum, J. communis, J. seravschanica, J. sabina, J. pseudosabina, J. pseudosabina subsp. turkestanica, and J. sibirica. We report here the chemical composition and innate immunomodulatory activity of these essential oils. Compositional analysis of the 16 samples of Juniper essential oils revealed similarities and differences between our analyses and those previously reported for essential oils from this species. Our studies represent the first analysis of essential oils isolated from the cones of four of these Juniper species. Several essential oil samples contained high levels of cedrol, which was fairly unique to three Juniper species from Kazakhstan. We found that these essential oils and pure (+)-cedrol induced intracellular Ca2+ mobilization in human neutrophils. Furthermore, pretreatment of human neutrophils and N-formyl peptide receptor 1 and 2 (FPR1 and FPR2) transfected HL60 cells with these essential oils or (+)-cedrol inhibited agonist-induced Ca2+ mobilization, suggesting these responses were desensitized by this pretreatment. In support of this conclusion, pretreatment with essential oils from J. seravschanica cones (containing 16.8% cedrol) or pure (+)-cedrol inhibited human neutrophil chemotaxis to N-formyl peptide. Finally, reverse pharmacophore mapping predicted several potential kinase targets for cedrol. Thus, our studies have identified cedrol as a novel neutrophil agonist that can desensitize cells to subsequent stimulation by N-formyl peptide.

scholarly journals Chemical Composition and Immunomodulatory Activity of Essential Oils from Rhododendron albiflorum

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3652
Author(s):  
Igor A. Schepetkin ◽  
Gulmira Özek ◽  
Temel Özek ◽  
Liliya N. Kirpotina ◽  
Andrei I. Khlebnikov ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Essential Oils ◽  
Neutrophil Migration ◽  
Compositional Analysis ◽  
Microglial Cells ◽  
Formyl Peptide Receptor ◽  
Human Neutrophils ◽  
Immunomodulatory Activity ◽  
Hl60 Cells ◽  
Formyl Peptide

Rhododendron (Ericaceae) extracts contain flavonoids, chromones, terpenoids, steroids, and essential oils and are used in traditional ethnobotanical medicine. However, little is known about the immunomodulatory activity of essential oils isolated from these plants. Thus, we isolated essential oils from the flowers and leaves of R. albiflorum (cascade azalea) and analyzed their chemical composition and innate immunomodulatory activity. Compositional analysis of flower (REOFl) versus leaf (REOLv) essential oils revealed significant differences. REOFl was comprised mainly of monoterpenes (92%), whereas sesquiterpenes were found in relatively low amounts. In contrast, REOLv was primarily composed of sesquiterpenes (90.9%), with a small number of monoterpenes. REOLv and its primary sesquiterpenes (viridiflorol, spathulenol, curzerene, and germacrone) induced intracellular Ca2+ mobilization in human neutrophils, C20 microglial cells, and HL60 cells transfected with N-formyl peptide receptor 1 (FPR1) or FPR2. On the other hand, pretreatment with these essential oils or component compounds inhibited agonist-induced Ca2+ mobilization and chemotaxis in human neutrophils and agonist-induced Ca2+ mobilization in microglial cells and FPR-transfected HL60 cells, indicating that the direct effect of these compounds on [Ca2+]i desensitized the cells to subsequent agonist activation. Reverse pharmacophore mapping suggested several potential kinase targets for these compounds; however, these targets were not supported by kinase binding assays. Our results provide a cellular and molecular basis to explain at least part of the beneficial immunotherapeutic properties of the R. albiflorum essential oils and suggest that essential oils from leaves of this plant may be effective in modulating some innate immune responses, possibly by inhibition of neutrophil migration.

scholarly journals Aurantiamide-related dipeptide derivatives are formyl peptide receptor 1 antagonists

MedChemComm ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 2078-2088
Author(s):  
Margherita Mastromarino ◽  
Liliya N. Kirpotina ◽  
Igor A. Schepetkin ◽  
Mark T. Quinn ◽  
Enza Lacivita ◽  
...  
Keyword(s):  
Formyl Peptide Receptor ◽  
Neutrophil Chemotaxis ◽  
Peptide Receptor ◽  
Formyl Peptide

Aurantiamide is a useful scaffold to develop promising FPR1 antagonists capable of inhibiting neutrophil chemotaxis.

Cloning of a cDNA encoding a receptor related to the formyl peptide receptor of human neutrophils

Gene ◽  
1992 ◽  
Vol 118 (2) ◽  
pp. 303-304 ◽  
Author(s):  
H.Daniel Perez ◽  
Richard Holmes ◽  
Edward Kelly ◽  
John McClary ◽  
William H. Andrews
Keyword(s):  
Formyl Peptide Receptor ◽  
Human Neutrophils ◽  
Peptide Receptor ◽  
Formyl Peptide

scholarly journals N-Formyl peptide receptor subtypes in human neutrophils activate l-plastin phosphorylation through different signal transduction intermediates

2004 ◽  
Vol 377 (2) ◽  
pp. 469-477 ◽  
Author(s):  
Marie-Hélène PACLET ◽  
Clare DAVIS ◽  
Peter KOTSONIS ◽  
Jasminka GODOVAC-ZIMMERMANN ◽  
Anthony W. SEGAL ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Formyl Peptide Receptor ◽  
Actin Binding ◽  
Human Neutrophils ◽  
Receptor Subtypes ◽  
Peptide Receptor ◽  
High Affinity ◽  
Formyl Peptide ◽  
Fmlp Receptor ◽  
Phosphoinositide 3 Kinase

We investigated the coupling of the fMLP (N-formyl-l-methionyl-l-leucyl-l-phenylalanine; ‘chemotactic peptide’) receptor with phosphorylation of the actin-binding protein l-plastin in neutrophils. Using two-dimensional IEF (isoelectric focusing)/PAGE and MALDI–TOF (matrix-assisted laser desorption ionization–time-of-flight)-MS, l-plastin was identified as a major phosphoprotein in fMLP-stimulated neutrophils whose phosphorylation was dependent on phosphoinositide 3-kinase, PLD (phospholipase D) and PKC (protein kinase C) activity. Two fMLP receptor subtypes were identified in neutrophils, characterized by a distinct sensitivity to fMLP and antagonistic peptides. Both receptor subtypes induced the phosphorylation of l-plastin. l-plastin phosphorylation induced by low-affinity fMLP receptors involves an action of phosphoinositide 3-kinase, PLD and PKC isotypes. In contrast, none of these intermediates are utilized by high-affinity fMLP receptors in the phosphorylation of l-plastin. However, the PKC inhibitor Ro-31-8220 inhibits l-plastin phosphorylation induced by the high-affinity fMLP receptor. Thus, an as yet unknown Ro-31-8220-sensitive kinase regulates l-plastin phosphorylation in response to the high-affinity fMLP receptor. The results suggest a model in which receptor subtypes induce a similar endpoint event through different signal-transduction intermediates. This may be relevant in the context of cell migration in which one receptor subpopulation may become desensitized in a concentration gradient of chemoattractant.

scholarly journals Development, characterisation and in vitro evaluation of lanthanide-based FPR2/ALX-targeted imaging probes

2019 ◽  
Vol 48 (44) ◽  
pp. 16764-16775 ◽  
Author(s):  
Tamara Boltersdorf ◽  
Junaid Ansari ◽  
Elena Y. Senchenkova ◽  
Lijun Jiang ◽  
Andrew J. P. White ◽  
...  
Keyword(s):  
Lanthanide Complexes ◽  
Formyl Peptide Receptor ◽  
Human Neutrophils ◽  
Targeted Imaging ◽  
In Vitro Evaluation ◽  
Peptide Receptor ◽  
Imaging Probes ◽  
Formyl Peptide

Formyl Peptide Receptor (FPR)-targeted lanthanide complexes with long-lived emission in stimulated human neutrophils.

The synthetic chemoattractant Trp-Lys-Tyr-Met-Val-DMet activates neutrophils preferentially through the lipoxin A4 receptor

Blood ◽  
2000 ◽  
Vol 95 (5) ◽  
pp. 1810-1818 ◽  
Author(s):  
Claes Dahlgren ◽  
Thierry Christophe ◽  
Francois Boulay ◽  
Phoebus N. Madianos ◽  
Marie J. Rabiet ◽  
...  
Keyword(s):  
Formyl Peptide Receptor ◽  
Neutrophil Chemotaxis ◽  
Lipoxin A4 ◽  
Independent Manner ◽  
Effector Functions ◽  
Peptide Receptor ◽  
Formyl Peptide ◽  
Complement Receptor 3 ◽  
Neutrophil Response ◽  
Cyclosporin H

A D-methionine–containing peptide, Trp-Lys-Tyr-Met-Val-D-Met-NH2 (WKYMVm), featuring a unique receptor specificity was investigated with respect to its ability to activate neutrophil effector functions. The peptide was found to be more potent than the N-formylated peptide N-formyl-Met-Leu-Phe (fMLF) at inducing neutrophil chemotaxis, mobilization of neutrophil complement receptor 3 (CR3), and activation of the neutrophil NADPH-oxidase. The fact that binding of fML[3H]F was inhibited by both fMLF and WKYMVm suggests that N-formyl peptide receptor (FPR) is shared by these peptides. However, the neutrophil response induced by the WKYMVm peptide was insensitive to the fMLF antagonists, cyclosporin H, and Boc-FLFLF that specifically block the function of the FPR. These results suggest that even though WKYMVm may bind FPR the cells are activated preferentially through a receptor distinct from the FPR. Using transfected HL-60 cells expressing either the FPR or its neutrophil homologue FPRL1, also referred to as LXA4R because it has been shown to bind lipoxin A4, we show that WKYMVm is about 300-fold more active at mobilizing intracellular calcium through FPRL1 than through FPR. The WKYMVm activates FPRL1-expressing cells in a cyclosporin H-independent manner with an EC50 of around 75 pmol/L, whereas it activates FPR-expressing cells with an EC50 of around 25 nmol/L. The observation that exudated cells are primed in their response to WKYMVm suggests that FPRL1/LXA4R like FPR is stored in mobilizable organelles.

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