Adeno-associated Virus Vector-mediated Interleukin-10 Induction Prevents Vascular Inflammation in a Murine Model of Kawasaki Disease

Scientific Reports
Jun NakamuraMasafumi Takahashi

Abstract

Kawasaki disease (KD), which is the leading cause of pediatric heart disease, is characterized by coronary vasculitis and subsequent aneurysm formation. Although intravenous immunoglobulin therapy is effective for reducing aneurysm formation, a certain number of patients are resistant to this therapy. Because interleukin-10 (IL-10) was identified as a negative regulator of cardiac inflammation in a murine model of KD induced by Candida albicans water-soluble fraction (CAWS), we investigated the effect of IL-10 supplementation in CAWS-induced vasculitis. Mice were injected intramuscularly with adeno-associated virus (AAV) vector encoding IL-10, then treated with CAWS. The induction of AAV-mediated IL-10 (AAV-IL-10) significantly attenuated the vascular inflammation and fibrosis in the aortic root and coronary artery, resulting in the improvement of cardiac dysfunction and lethality. The predominant infiltrating inflammatory cells in the vascular walls were Dectin-2+CD11b+ macrophages. In vitro experiments revealed that granulocyte/macrophage colony-stimulating factor (GM-CSF) induced Dectin-2 expression in bone marrow-derived macrophages and enhanced the CAWS-induced production of tumor necrosis factor-α (TNF-α) and IL-6. IL-10 ...Continue Reading

References

Feb 1, 1997·International Archives of Allergy and Immunology·J HiraoT Ichimura
Aug 14, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Noriko N MiuraNaohito Ohno
Aug 26, 2009·The Journal of Experimental Medicine·Matthew J RobinsonCaetano Reis e Sousa
Mar 27, 2010·Circulation Journal : Official Journal of the Japanese Circulation Society·Ken-Pen WengLuo-Ping Ger
Dec 1, 2010·Cytokine & Growth Factor Reviews·Robert SabatJens Geginat
Dec 7, 2010·The Journal of Pediatrics·Mary Beth SonJane W Newburger
Jun 17, 2011·International Immunology·Shinobu Saijo, Yoichiro Iwakura
Apr 7, 2012·Nature·Jennifer Frazer
Mar 25, 2014·Journal of Clinical Laboratory Analysis·Ying-Ju LinFuu-Jen Tsai
May 21, 2014·Proceedings of the National Academy of Sciences of the United States of America·Xavier RodóJosep-Anton Morguí
Jul 22, 2014·Pediatric Rheumatology Online Journal·Ashley ShaffermanRandy Q Cron
Nov 8, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Fumitake UsuiMasafumi Takahashi
Apr 4, 2015·Arteriosclerosis, Thrombosis, and Vascular Biology·Yoshitomo MotomuraSho Yamasaki
Jun 24, 2015·Expert Review of Clinical Immunology·Jane C Burns, Alessandra Franco
Mar 5, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Daiko WakitaMoshe Arditi
Apr 9, 2016·Journal of the American College of Cardiology·Jane W NewburgerJane C Burns
Jul 22, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Fábio V MarinhoSergio Costa Oliveira
Aug 11, 2016·Drug Discovery Today·Caroline GaleottiJagadeesh Bayry
Aug 21, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Patricia Castillo, Jay K Kolls
Sep 7, 2016·The Journal of Experimental Medicine·Angus T StockIan P Wicks
Apr 13, 2017·Frontiers in Pharmacology·Perrine Dusser, Isabelle Koné-Paut
Jul 29, 2017·Heart·Kara J DenbyLarry W Markham

❮ Previous
Next ❯

Citations

Mar 13, 2020·Biological & Pharmaceutical Bulletin·Chiho YanaiYoshiyuki Adachi
May 28, 2020·Nature Reviews. Rheumatology·Magali Noval Rivas, Moshe Arditi
Jul 17, 2020·Frontiers in Cardiovascular Medicine·Mark Daniel Hicar
Oct 6, 2020·Frontiers in Immunology·María Tristán-ManzanoFrancisco Martin
Sep 22, 2020·Current Opinion in Pharmacology·Rui Long ZhangBetty Yuen-Kwan Law
Dec 15, 2019·Journal of Molecular and Cellular Cardiology·Fumiya AnzaiMasafumi Takahashi
Jun 9, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yu LunFeng Lin

❮ Previous
Next ❯

Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
flow cytometry
enzyme-linked immunosorbent assay

Software Mentioned

GraphPad Prism
Adobe Photoshop
FlowJo

Related Concepts

Related Feeds

Cardiovascular Inflammation

Inflammation plays a significant role in the development of cardiovascular diseases, an understanding of these endogenous processes is critical for evaluating the risks and potential treatment strategies. Discover the latest research on cardiovascular inflammation here.

Cell-Type-Specific Viral Vectors (ASM)

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Candida albicans

Candida albicans is an opportunistic, fungal pathogen of humans that frequently causes superficial infections of oral and vaginal mucosal surfaces of debilitated and susceptible individuals. Discover the latest research on Candida albicans here.

AAV-based Gene Therapy

Adeno-associated virus (AAV)-based gene therapy is a biological vector that is being researched to be used as a potential therapeutic option. This gene therapy is designed to insert fragments of DNA into targeted cells to help treat diseases, such as hemophilia a. Discover the latest research on AAV-based gene therapy here.

Candidiasis

Candidiasis is a common fungal infection caused by Candida and it can affect many parts for the body including mucosal membranes as well as the gastrointestinal, urinary, and respiratory tracts. Here is the latest research.

Candidiasis (ASM)

Candidiasis is a common fungal infection caused by Candida and it can affect many parts for the body including mucosal membranes as well as the gastrointestinal, urinary, and respiratory tracts. Here is the latest research.

CSF & Lymphatic System

This feed focuses on Cerebral Spinal Fluid (CSF) and the lymphatic system. Discover the latest papers using imaging techniques to track CSF outflow into the lymphatic system in animal models.

Cell-Type-Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Cell-Type Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Aneurysm

Aneurysms are outward distensions or bulges that occurs in a weakened wall of blood vessels. Discover the latest research on aneurysms here.