MicroRNA-223 Regulates the Development of Cardiovascular Lesions in LCWE-Induced Murine Kawasaki Disease Vasculitis by Repressing the NLRP3 Inflammasome
Kawasaki disease (KD), an acute febrile childhood illness and systemic vasculitis of unknown etiology, is the leading cause of acquired heart disease among children. Experimental data from murine models of KD vasculitis and transcriptomics data generated from whole blood of KD patients indicate the...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2021.662953/full |
| _version_ | 1818672264404533248 |
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| author | Daisuke Maruyama Begüm Kocatürk Youngho Lee Masanori Abe Malcolm Lane Debbie Moreira Shuang Chen Shuang Chen Michael C. Fishbein Rebecca A. Porritt Rebecca A. Porritt Magali Noval Rivas Magali Noval Rivas Moshe Arditi Moshe Arditi |
| author_facet | Daisuke Maruyama Begüm Kocatürk Youngho Lee Masanori Abe Malcolm Lane Debbie Moreira Shuang Chen Shuang Chen Michael C. Fishbein Rebecca A. Porritt Rebecca A. Porritt Magali Noval Rivas Magali Noval Rivas Moshe Arditi Moshe Arditi |
| author_sort | Daisuke Maruyama |
| collection | DOAJ |
| description | Kawasaki disease (KD), an acute febrile childhood illness and systemic vasculitis of unknown etiology, is the leading cause of acquired heart disease among children. Experimental data from murine models of KD vasculitis and transcriptomics data generated from whole blood of KD patients indicate the involvement of the NLRP3 inflammasome and interleukin-1 (IL-1) signaling in KD pathogenesis. MicroRNA-223 (miR-223) is a negative regulator of NLRP3 activity and IL-1β production, and its expression has been reported to be upregulated during acute human KD; however, the specific role of miR-223 during KD vasculitis remains unknown. Here, using the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis, we demonstrate increased miR-223 expression in LCWE-induced cardiovascular lesions. Compared with control WT mice, LCWE-injected miR-223-deficient mice (miR223−/y) developed more severe coronary arteritis and aortitis, as well as more pronounced abdominal aorta aneurysms and dilations. The enhanced cardiovascular lesions and KD vasculitis observed in LCWE-injected miR223−/y mice correlated with increased NLRP3 inflammasome activity and elevated IL-1β production, indicating that miR-223 limits cardiovascular lesion development by downmodulating NLRP3 inflammasome activity. Collectively, our data reveal a previously unappreciated role of miR-223 in regulating innate immune responses and in limiting KD vasculitis and its cardiovascular lesions by constraining the NLRP3 inflammasome and the IL-1β pathway. These data also suggest that miR-223 expression may be used as a marker for KD vasculitis pathogenesis and provide a novel therapeutic target. |
| first_indexed | 2024-12-17T07:37:08Z |
| format | Article |
| id | doaj.art-98fba64e12d9447c86fc29af82429d09 |
| institution | Directory Open Access Journal |
| issn | 2296-2360 |
| language | English |
| last_indexed | 2024-12-17T07:37:08Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| spelling | doaj.art-98fba64e12d9447c86fc29af82429d092022-12-21T21:58:17ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602021-05-01910.3389/fped.2021.662953662953MicroRNA-223 Regulates the Development of Cardiovascular Lesions in LCWE-Induced Murine Kawasaki Disease Vasculitis by Repressing the NLRP3 InflammasomeDaisuke Maruyama0Begüm Kocatürk1Youngho Lee2Masanori Abe3Malcolm Lane4Debbie Moreira5Shuang Chen6Shuang Chen7Michael C. Fishbein8Rebecca A. Porritt9Rebecca A. Porritt10Magali Noval Rivas11Magali Noval Rivas12Moshe Arditi13Moshe Arditi14Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesDivision of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesDivision of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesDivision of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesDivision of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesDivision of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesDivision of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesDepartment of Biomedical Sciences, Infectious and Immunological Diseases Research Center, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesDepartment of Pathology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United StatesDivision of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesDepartment of Biomedical Sciences, Infectious and Immunological Diseases Research Center, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesDivision of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesDepartment of Biomedical Sciences, Infectious and Immunological Diseases Research Center, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesDivision of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesDepartment of Biomedical Sciences, Infectious and Immunological Diseases Research Center, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesKawasaki disease (KD), an acute febrile childhood illness and systemic vasculitis of unknown etiology, is the leading cause of acquired heart disease among children. Experimental data from murine models of KD vasculitis and transcriptomics data generated from whole blood of KD patients indicate the involvement of the NLRP3 inflammasome and interleukin-1 (IL-1) signaling in KD pathogenesis. MicroRNA-223 (miR-223) is a negative regulator of NLRP3 activity and IL-1β production, and its expression has been reported to be upregulated during acute human KD; however, the specific role of miR-223 during KD vasculitis remains unknown. Here, using the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis, we demonstrate increased miR-223 expression in LCWE-induced cardiovascular lesions. Compared with control WT mice, LCWE-injected miR-223-deficient mice (miR223−/y) developed more severe coronary arteritis and aortitis, as well as more pronounced abdominal aorta aneurysms and dilations. The enhanced cardiovascular lesions and KD vasculitis observed in LCWE-injected miR223−/y mice correlated with increased NLRP3 inflammasome activity and elevated IL-1β production, indicating that miR-223 limits cardiovascular lesion development by downmodulating NLRP3 inflammasome activity. Collectively, our data reveal a previously unappreciated role of miR-223 in regulating innate immune responses and in limiting KD vasculitis and its cardiovascular lesions by constraining the NLRP3 inflammasome and the IL-1β pathway. These data also suggest that miR-223 expression may be used as a marker for KD vasculitis pathogenesis and provide a novel therapeutic target.https://www.frontiersin.org/articles/10.3389/fped.2021.662953/fullmiR-223IL-1 betaKawasaki diseasevasculitisNLRP3LCWE |
| spellingShingle | Daisuke Maruyama Begüm Kocatürk Youngho Lee Masanori Abe Malcolm Lane Debbie Moreira Shuang Chen Shuang Chen Michael C. Fishbein Rebecca A. Porritt Rebecca A. Porritt Magali Noval Rivas Magali Noval Rivas Moshe Arditi Moshe Arditi MicroRNA-223 Regulates the Development of Cardiovascular Lesions in LCWE-Induced Murine Kawasaki Disease Vasculitis by Repressing the NLRP3 Inflammasome Frontiers in Pediatrics miR-223 IL-1 beta Kawasaki disease vasculitis NLRP3 LCWE |
| title | MicroRNA-223 Regulates the Development of Cardiovascular Lesions in LCWE-Induced Murine Kawasaki Disease Vasculitis by Repressing the NLRP3 Inflammasome |
| title_full | MicroRNA-223 Regulates the Development of Cardiovascular Lesions in LCWE-Induced Murine Kawasaki Disease Vasculitis by Repressing the NLRP3 Inflammasome |
| title_fullStr | MicroRNA-223 Regulates the Development of Cardiovascular Lesions in LCWE-Induced Murine Kawasaki Disease Vasculitis by Repressing the NLRP3 Inflammasome |
| title_full_unstemmed | MicroRNA-223 Regulates the Development of Cardiovascular Lesions in LCWE-Induced Murine Kawasaki Disease Vasculitis by Repressing the NLRP3 Inflammasome |
| title_short | MicroRNA-223 Regulates the Development of Cardiovascular Lesions in LCWE-Induced Murine Kawasaki Disease Vasculitis by Repressing the NLRP3 Inflammasome |
| title_sort | microrna 223 regulates the development of cardiovascular lesions in lcwe induced murine kawasaki disease vasculitis by repressing the nlrp3 inflammasome |
| topic | miR-223 IL-1 beta Kawasaki disease vasculitis NLRP3 LCWE |
| url | https://www.frontiersin.org/articles/10.3389/fped.2021.662953/full |
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