Angiotensin AT2-receptor induced interleukin-10 attenuates neuromyelitis optica spectrum disorder-like pathology

Reza M. H. Khorooshi, Emil Ulrikkaholm Tofte-Hansen, Camilla Tygesen, Roser Montañana Rosell, Hannah Liska Limburg, Joanna Marczynska, Nasrin Asgari, Muscha Steckelings, Trevor Owens*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing inflammatory central nervous system (CNS) disease for which there is no cure. Immunoglobulin G autoantibodies specific for the water channel aquaporin-4 are a serum biomarker, believed to induce complement-dependent astrocyte damage with secondary demyelination. Objective: To investigate the effect of angiotensin AT2 receptor (AT2R) stimulation on NMOSD-like pathology and its underlying mechanism. Methods: NMOSD-like pathology was induced in mice by intracerebral injection of immunoglobulin-G isolated from NMOSD patient serum, with complement. This mouse model produces the characteristic histological features of NMOSD. A specific AT2R agonist, Compound 21 (C21), was given intracerebrally at day 0 and by intrathecal injection at day 2. Results: Loss of aquaporin-4 and glial fibrillary acidic protein was attenuated by treatment with C21. Administration of C21 induced mRNA for interleukin-10 in the brain. NMOSD-like pathology was exacerbated in interleukin-10-deficient mice, suggesting a protective role. C21 treatment did not attenuate NMOSD-like pathology in interleukin-10-deficient mice, indicating that the protective effect of AT2R stimulation was dependent on interleukin-10. Conclusion: Our findings identify AT2R as a novel potential therapeutic target for the treatment of NMOSD. Interleukin-10 signaling is an essential part of the protective mechanism counteracting NMOSD pathology.

Original languageEnglish
JournalMultiple Sclerosis Journal
ISSN1352-4585
DOIs
Publication statusPublished - 2019

Fingerprint

Angiotensin Type 2 Receptor
Neuromyelitis Optica
Interleukin-10
Pathology
Central Nervous System Diseases
Glial Fibrillary Acidic Protein
Demyelinating Diseases
Serum

Keywords

  • Compound 21
  • IL-10
  • Neuromyelitis optica spectrum disorder
  • angiotensin AT2 receptor
  • astrocytopathology

Cite this

@article{f15fab51f4da4689bd21722f847a5421,
title = "Angiotensin AT2-receptor induced interleukin-10 attenuates neuromyelitis optica spectrum disorder-like pathology",
abstract = "Background: Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing inflammatory central nervous system (CNS) disease for which there is no cure. Immunoglobulin G autoantibodies specific for the water channel aquaporin-4 are a serum biomarker, believed to induce complement-dependent astrocyte damage with secondary demyelination. Objective: To investigate the effect of angiotensin AT2 receptor (AT2R) stimulation on NMOSD-like pathology and its underlying mechanism. Methods: NMOSD-like pathology was induced in mice by intracerebral injection of immunoglobulin-G isolated from NMOSD patient serum, with complement. This mouse model produces the characteristic histological features of NMOSD. A specific AT2R agonist, Compound 21 (C21), was given intracerebrally at day 0 and by intrathecal injection at day 2. Results: Loss of aquaporin-4 and glial fibrillary acidic protein was attenuated by treatment with C21. Administration of C21 induced mRNA for interleukin-10 in the brain. NMOSD-like pathology was exacerbated in interleukin-10-deficient mice, suggesting a protective role. C21 treatment did not attenuate NMOSD-like pathology in interleukin-10-deficient mice, indicating that the protective effect of AT2R stimulation was dependent on interleukin-10. Conclusion: Our findings identify AT2R as a novel potential therapeutic target for the treatment of NMOSD. Interleukin-10 signaling is an essential part of the protective mechanism counteracting NMOSD pathology.",
keywords = "Compound 21, IL-10, Neuromyelitis optica spectrum disorder, angiotensin AT2 receptor, astrocytopathology",
author = "Khorooshi, {Reza M. H.} and Tofte-Hansen, {Emil Ulrikkaholm} and Camilla Tygesen and {Monta{\~n}ana Rosell}, Roser and Limburg, {Hannah Liska} and Joanna Marczynska and Nasrin Asgari and Muscha Steckelings and Trevor Owens",
year = "2019",
doi = "10.1177/1352458519860327",
language = "English",
journal = "Multiple Sclerosis Journal",
issn = "1352-4585",
publisher = "SAGE Publications",

}

Angiotensin AT2-receptor induced interleukin-10 attenuates neuromyelitis optica spectrum disorder-like pathology. / Khorooshi, Reza M. H.; Tofte-Hansen, Emil Ulrikkaholm; Tygesen, Camilla; Montañana Rosell, Roser; Limburg, Hannah Liska; Marczynska, Joanna; Asgari, Nasrin; Steckelings, Muscha; Owens, Trevor.

In: Multiple Sclerosis Journal, 2019.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Angiotensin AT2-receptor induced interleukin-10 attenuates neuromyelitis optica spectrum disorder-like pathology

AU - Khorooshi, Reza M. H.

AU - Tofte-Hansen, Emil Ulrikkaholm

AU - Tygesen, Camilla

AU - Montañana Rosell, Roser

AU - Limburg, Hannah Liska

AU - Marczynska, Joanna

AU - Asgari, Nasrin

AU - Steckelings, Muscha

AU - Owens, Trevor

PY - 2019

Y1 - 2019

N2 - Background: Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing inflammatory central nervous system (CNS) disease for which there is no cure. Immunoglobulin G autoantibodies specific for the water channel aquaporin-4 are a serum biomarker, believed to induce complement-dependent astrocyte damage with secondary demyelination. Objective: To investigate the effect of angiotensin AT2 receptor (AT2R) stimulation on NMOSD-like pathology and its underlying mechanism. Methods: NMOSD-like pathology was induced in mice by intracerebral injection of immunoglobulin-G isolated from NMOSD patient serum, with complement. This mouse model produces the characteristic histological features of NMOSD. A specific AT2R agonist, Compound 21 (C21), was given intracerebrally at day 0 and by intrathecal injection at day 2. Results: Loss of aquaporin-4 and glial fibrillary acidic protein was attenuated by treatment with C21. Administration of C21 induced mRNA for interleukin-10 in the brain. NMOSD-like pathology was exacerbated in interleukin-10-deficient mice, suggesting a protective role. C21 treatment did not attenuate NMOSD-like pathology in interleukin-10-deficient mice, indicating that the protective effect of AT2R stimulation was dependent on interleukin-10. Conclusion: Our findings identify AT2R as a novel potential therapeutic target for the treatment of NMOSD. Interleukin-10 signaling is an essential part of the protective mechanism counteracting NMOSD pathology.

AB - Background: Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing inflammatory central nervous system (CNS) disease for which there is no cure. Immunoglobulin G autoantibodies specific for the water channel aquaporin-4 are a serum biomarker, believed to induce complement-dependent astrocyte damage with secondary demyelination. Objective: To investigate the effect of angiotensin AT2 receptor (AT2R) stimulation on NMOSD-like pathology and its underlying mechanism. Methods: NMOSD-like pathology was induced in mice by intracerebral injection of immunoglobulin-G isolated from NMOSD patient serum, with complement. This mouse model produces the characteristic histological features of NMOSD. A specific AT2R agonist, Compound 21 (C21), was given intracerebrally at day 0 and by intrathecal injection at day 2. Results: Loss of aquaporin-4 and glial fibrillary acidic protein was attenuated by treatment with C21. Administration of C21 induced mRNA for interleukin-10 in the brain. NMOSD-like pathology was exacerbated in interleukin-10-deficient mice, suggesting a protective role. C21 treatment did not attenuate NMOSD-like pathology in interleukin-10-deficient mice, indicating that the protective effect of AT2R stimulation was dependent on interleukin-10. Conclusion: Our findings identify AT2R as a novel potential therapeutic target for the treatment of NMOSD. Interleukin-10 signaling is an essential part of the protective mechanism counteracting NMOSD pathology.

KW - Compound 21

KW - IL-10

KW - Neuromyelitis optica spectrum disorder

KW - angiotensin AT2 receptor

KW - astrocytopathology

U2 - 10.1177/1352458519860327

DO - 10.1177/1352458519860327

M3 - Journal article

JO - Multiple Sclerosis Journal

JF - Multiple Sclerosis Journal

SN - 1352-4585

ER -