Differentiation of human macrophages with anaphylatoxin C3a impairs alternative M2 polarization and decreases lipopolysaccharide-induced cytokine secretion

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Differentiation of human macrophages with anaphylatoxin C3a impairs alternative M2 polarization and decreases lipopolysaccharide-induced cytokine secretion. / Mogilenko, Denis A.; Danko, Katerina; Larionova, Ekaterina E.; Shavva, Vladimir S.; Kudriavtsev, Igor V.; Nekrasova, Ekaterina V.; Burnusuz, Alexandra V.; Gorbunov, Nikolay P.; Trofimov, Alexander V.; Zhakhov, Alexander V.; Ivanov, Igor A.; Orlov, Sergey V.

In: Immunology and Cell Biology, Vol. 100, No. 3, 03.2022, p. 186-204.

Research output: Contribution to journal › Article › peer-review

Author

Mogilenko, Denis A. ; Danko, Katerina ; Larionova, Ekaterina E. ; Shavva, Vladimir S. ; Kudriavtsev, Igor V. ; Nekrasova, Ekaterina V. ; Burnusuz, Alexandra V. ; Gorbunov, Nikolay P. ; Trofimov, Alexander V. ; Zhakhov, Alexander V. ; Ivanov, Igor A. ; Orlov, Sergey V. / Differentiation of human macrophages with anaphylatoxin C3a impairs alternative M2 polarization and decreases lipopolysaccharide-induced cytokine secretion. In: Immunology and Cell Biology. 2022 ; Vol. 100, No. 3. pp. 186-204.

BibTeX

@article{ade7044d2367444b914fb56b5810a278,

title = "Differentiation of human macrophages with anaphylatoxin C3a impairs alternative M2 polarization and decreases lipopolysaccharide-induced cytokine secretion",

abstract = "Anaphylatoxin C3a is a small signaling polypeptide that is generated during complement activation. C3a is involved in the regulation of various innate and adaptive immune system processes; however, the role of C3a in macrophage differentiation and polarization is poorly elucidated. Here we showed that C3a impairs alternative M2 polarization of human macrophages and suppressed CD206, IL1Ra and CCL22 expression. C3a leads to a decrease of nuclear receptor PPARγ expression via the ERK1/2 signaling pathway, resulting in repressed PPARγ-dependent activation of CD36, FABP4 and LXRα genes and blunted response to an LXR ligand TO901317. Using small interfering RNA and agonist/antagonist approaches we showed that C3a decreases CD206, IL1Ra and CCL22 transcription at least partly in a PPARγ-dependent manner in M2 macrophages. Moreover, C3a impairs efferocytosis by M2 macrophages and inhibits their migratory activity. By contrast, macrophages treated with C3a during differentiation show blunted response to lipopolysaccharide stimulation owing to downregulation of TLR4 and lipid raft content. At the same time, differentiation of macrophages with C3a does not change M1 polarization in interferon gamma (IFNγ) and IFNγ + lipopolysaccharide–treated macrophages. These data provide a novel role of complement system and C3a in the regulation of M2 macrophage polarizations and suggest crosstalk between C3a, TLR4, PPARγ and LXR signaling pathways.",

keywords = "Anaphylatoxin C3a, LXR, M1 macrophages, M2 macrophages, PPARγ, TLR4, Lipopolysaccharides/metabolism, PPAR gamma/metabolism, Humans, Macrophages/metabolism, Interferon-gamma/metabolism, Toll-Like Receptor 4/metabolism, Anaphylatoxins/metabolism",

author = "Mogilenko, {Denis A.} and Katerina Danko and Larionova, {Ekaterina E.} and Shavva, {Vladimir S.} and Kudriavtsev, {Igor V.} and Nekrasova, {Ekaterina V.} and Burnusuz, {Alexandra V.} and Gorbunov, {Nikolay P.} and Trofimov, {Alexander V.} and Zhakhov, {Alexander V.} and Ivanov, {Igor A.} and Orlov, {Sergey V.}",

note = "Publisher Copyright: {\textcopyright} 2022 Australian and New Zealand Society for Immunology, Inc.",

year = "2022",

month = mar,

doi = "10.1111/imcb.12534",

language = "English",

volume = "100",

pages = "186--204",

journal = "Immunology and Cell Biology",

issn = "0818-9641",

publisher = "Springer Nature",

number = "3",

}

RIS

TY - JOUR

T1 - Differentiation of human macrophages with anaphylatoxin C3a impairs alternative M2 polarization and decreases lipopolysaccharide-induced cytokine secretion

AU - Mogilenko, Denis A.

AU - Danko, Katerina

AU - Larionova, Ekaterina E.

AU - Shavva, Vladimir S.

AU - Kudriavtsev, Igor V.

AU - Nekrasova, Ekaterina V.

AU - Burnusuz, Alexandra V.

AU - Gorbunov, Nikolay P.

AU - Trofimov, Alexander V.

AU - Zhakhov, Alexander V.

AU - Ivanov, Igor A.

AU - Orlov, Sergey V.

PY - 2022/3

Y1 - 2022/3

N2 - Anaphylatoxin C3a is a small signaling polypeptide that is generated during complement activation. C3a is involved in the regulation of various innate and adaptive immune system processes; however, the role of C3a in macrophage differentiation and polarization is poorly elucidated. Here we showed that C3a impairs alternative M2 polarization of human macrophages and suppressed CD206, IL1Ra and CCL22 expression. C3a leads to a decrease of nuclear receptor PPARγ expression via the ERK1/2 signaling pathway, resulting in repressed PPARγ-dependent activation of CD36, FABP4 and LXRα genes and blunted response to an LXR ligand TO901317. Using small interfering RNA and agonist/antagonist approaches we showed that C3a decreases CD206, IL1Ra and CCL22 transcription at least partly in a PPARγ-dependent manner in M2 macrophages. Moreover, C3a impairs efferocytosis by M2 macrophages and inhibits their migratory activity. By contrast, macrophages treated with C3a during differentiation show blunted response to lipopolysaccharide stimulation owing to downregulation of TLR4 and lipid raft content. At the same time, differentiation of macrophages with C3a does not change M1 polarization in interferon gamma (IFNγ) and IFNγ + lipopolysaccharide–treated macrophages. These data provide a novel role of complement system and C3a in the regulation of M2 macrophage polarizations and suggest crosstalk between C3a, TLR4, PPARγ and LXR signaling pathways.

AB - Anaphylatoxin C3a is a small signaling polypeptide that is generated during complement activation. C3a is involved in the regulation of various innate and adaptive immune system processes; however, the role of C3a in macrophage differentiation and polarization is poorly elucidated. Here we showed that C3a impairs alternative M2 polarization of human macrophages and suppressed CD206, IL1Ra and CCL22 expression. C3a leads to a decrease of nuclear receptor PPARγ expression via the ERK1/2 signaling pathway, resulting in repressed PPARγ-dependent activation of CD36, FABP4 and LXRα genes and blunted response to an LXR ligand TO901317. Using small interfering RNA and agonist/antagonist approaches we showed that C3a decreases CD206, IL1Ra and CCL22 transcription at least partly in a PPARγ-dependent manner in M2 macrophages. Moreover, C3a impairs efferocytosis by M2 macrophages and inhibits their migratory activity. By contrast, macrophages treated with C3a during differentiation show blunted response to lipopolysaccharide stimulation owing to downregulation of TLR4 and lipid raft content. At the same time, differentiation of macrophages with C3a does not change M1 polarization in interferon gamma (IFNγ) and IFNγ + lipopolysaccharide–treated macrophages. These data provide a novel role of complement system and C3a in the regulation of M2 macrophage polarizations and suggest crosstalk between C3a, TLR4, PPARγ and LXR signaling pathways.

KW - Anaphylatoxin C3a

KW - LXR

KW - M1 macrophages

KW - M2 macrophages

KW - PPARγ

KW - TLR4

KW - Lipopolysaccharides/metabolism

KW - PPAR gamma/metabolism

KW - Humans

KW - Macrophages/metabolism

KW - Interferon-gamma/metabolism

KW - Toll-Like Receptor 4/metabolism

KW - Anaphylatoxins/metabolism

UR - http://www.scopus.com/inward/record.url?scp=85125599784&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/55c31708-700d-355a-8692-13a716e77e57/

U2 - 10.1111/imcb.12534

DO - 10.1111/imcb.12534

M3 - Article

C2 - 35148436

AN - SCOPUS:85125599784

VL - 100

SP - 186

EP - 204

JO - Immunology and Cell Biology

JF - Immunology and Cell Biology

SN - 0818-9641

IS - 3

ER -

ID: 100884279