Inflammatory response modulation by epinephrine and norepinephrine

Relevance. Inflammation is a defense response of an organism to a pathogen. It appears in order to maintain homeostasis and is regulated by the immune, nervous, and endocrine systems. The hormones epinephrine and norepinephrine are produced in the adrenal medulla and in the brain, and are universal...

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Main Authors: Svetlana V. Guryanova, Artem S. Ferberg, Ilya A. Sigmatulin
Format: Article
Language:English
Published: Peoples’ Friendship University of Russia (RUDN University) 2023-12-01
Series:RUDN Journal of Medicine
Subjects:
Online Access:https://journals.rudn.ru/medicine/article/viewFile/36100/22523
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author Svetlana V. Guryanova
Artem S. Ferberg
Ilya A. Sigmatulin
author_facet Svetlana V. Guryanova
Artem S. Ferberg
Ilya A. Sigmatulin
author_sort Svetlana V. Guryanova
collection DOAJ
description Relevance. Inflammation is a defense response of an organism to a pathogen. It appears in order to maintain homeostasis and is regulated by the immune, nervous, and endocrine systems. The hormones epinephrine and norepinephrine are produced in the adrenal medulla and in the brain, and are universal messengers that trigger the transmission of nerve impulses at synapses, and also have a receptor-mediated effect on immunocompetent cells. The aim of this study was to investigate adrenergic pathway regulation of inflammation on the neutrophil granulocytes in the presence of activators of innate immunity receptors. Materials and Methods. Neutrophil granulocytes were obtained from peripheral blood of healthy volunteers in a density gradient of Histopaque 1077 and Histopaque 1119 (Sigma Aldrich, Steinheim, Germany), and cultured in the presence of LPS, GMDP, epinephrine and norepinephrine. The amount of human neutrophil peptides 1-3 (HNP1-3) was examined using an enzyme-linked immunosorbent assay; the gene expression of TLR4, NOD2, ATF3 and A20 was determined using RT-PCR. Results and Discussion. Norepinephrine (noradrenaline) was found to decrease the synthesis of human neutrophils peptides 1-3 (HNP 1-3 defensins, alone and in the combination with agonists of TLR4 and NOD2 receptors - LPS and GMDP respectively. It was found out that there was no a statistically significant effect of epinephrine (adrenaline) on the production of HNP 1-3, including when combined with LPS and GMDP. As a result of the study, an increase in the levels of expression of the genes TLR4, NOD2 and regulator of inflammatory reactions A20 both in LPS- and GMDP- induced neutrophil culture were uncovered, while ATF3 was increased only in LPS-induced neutrophil culture. Epinephrine demonstrated the absence of a statistically significant effect on the expression of the studied genes. While norepinephrine significantly increased the expression of A20 genes. Conclusion. The data obtained shows that norepinephrine can reduce the synthesis of HNP 1-3, including the one induced by LPS and GMDP. Moreover, the ability of norepinephrine to induce the expression of A20 may play a significant role in modulation of inflammation.
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spelling doaj.art-aa493768db66451c9908fb61eb28b36e2023-09-29T13:20:42ZengPeoples’ Friendship University of Russia (RUDN University)RUDN Journal of Medicine2313-02452313-02612023-12-0127332934110.22363/2313-0245-2023-27-3-329-34121122Inflammatory response modulation by epinephrine and norepinephrineSvetlana V. Guryanova0https://orcid.org/0000-0001-6186-2462Artem S. Ferberg1https://orcid.org/0009-0001-8107-089XIlya A. Sigmatulin2https://orcid.org/0009-0008-2254-6932M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic ChemistryMoscow State UniversityMoscow State UniversityRelevance. Inflammation is a defense response of an organism to a pathogen. It appears in order to maintain homeostasis and is regulated by the immune, nervous, and endocrine systems. The hormones epinephrine and norepinephrine are produced in the adrenal medulla and in the brain, and are universal messengers that trigger the transmission of nerve impulses at synapses, and also have a receptor-mediated effect on immunocompetent cells. The aim of this study was to investigate adrenergic pathway regulation of inflammation on the neutrophil granulocytes in the presence of activators of innate immunity receptors. Materials and Methods. Neutrophil granulocytes were obtained from peripheral blood of healthy volunteers in a density gradient of Histopaque 1077 and Histopaque 1119 (Sigma Aldrich, Steinheim, Germany), and cultured in the presence of LPS, GMDP, epinephrine and norepinephrine. The amount of human neutrophil peptides 1-3 (HNP1-3) was examined using an enzyme-linked immunosorbent assay; the gene expression of TLR4, NOD2, ATF3 and A20 was determined using RT-PCR. Results and Discussion. Norepinephrine (noradrenaline) was found to decrease the synthesis of human neutrophils peptides 1-3 (HNP 1-3 defensins, alone and in the combination with agonists of TLR4 and NOD2 receptors - LPS and GMDP respectively. It was found out that there was no a statistically significant effect of epinephrine (adrenaline) on the production of HNP 1-3, including when combined with LPS and GMDP. As a result of the study, an increase in the levels of expression of the genes TLR4, NOD2 and regulator of inflammatory reactions A20 both in LPS- and GMDP- induced neutrophil culture were uncovered, while ATF3 was increased only in LPS-induced neutrophil culture. Epinephrine demonstrated the absence of a statistically significant effect on the expression of the studied genes. While norepinephrine significantly increased the expression of A20 genes. Conclusion. The data obtained shows that norepinephrine can reduce the synthesis of HNP 1-3, including the one induced by LPS and GMDP. Moreover, the ability of norepinephrine to induce the expression of A20 may play a significant role in modulation of inflammation.https://journals.rudn.ru/medicine/article/viewFile/36100/22523innate immunitytlr4nod2lpsmuramyl peptidedefensinshuman neutrophil peptides 1-3epinephrinenorepinephrinecatecholamineinflammation regulation
spellingShingle Svetlana V. Guryanova
Artem S. Ferberg
Ilya A. Sigmatulin
Inflammatory response modulation by epinephrine and norepinephrine
RUDN Journal of Medicine
innate immunity
tlr4
nod2
lps
muramyl peptide
defensins
human neutrophil peptides 1-3
epinephrine
norepinephrine
catecholamine
inflammation regulation
title Inflammatory response modulation by epinephrine and norepinephrine
title_full Inflammatory response modulation by epinephrine and norepinephrine
title_fullStr Inflammatory response modulation by epinephrine and norepinephrine
title_full_unstemmed Inflammatory response modulation by epinephrine and norepinephrine
title_short Inflammatory response modulation by epinephrine and norepinephrine
title_sort inflammatory response modulation by epinephrine and norepinephrine
topic innate immunity
tlr4
nod2
lps
muramyl peptide
defensins
human neutrophil peptides 1-3
epinephrine
norepinephrine
catecholamine
inflammation regulation
url https://journals.rudn.ru/medicine/article/viewFile/36100/22523
work_keys_str_mv AT svetlanavguryanova inflammatoryresponsemodulationbyepinephrineandnorepinephrine
AT artemsferberg inflammatoryresponsemodulationbyepinephrineandnorepinephrine
AT ilyaasigmatulin inflammatoryresponsemodulationbyepinephrineandnorepinephrine