TNF-α-induced miR-155 regulates IL-6 signaling in rheumatoid synovial fibroblasts

Abstract Background MicroRNAs (miRNAs) are important regulators of a variety of inflammatory mediators. The present study was undertaken to elucidate the role of miRNAs in the rheumatoid cytokine network. Methods We analyzed miRNA expression in rheumatoid synovial fibroblasts (RASFs). miRNA array-ba...

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Main Authors: Kiyoshi Migita, Nozomi Iwanaga, Yasumori Izumi, Chieko Kawahara, Kenji Kumagai, Tadashi Nakamura, Tomohiro Koga, Atsushi Kawakami
Format: Article
Language:English
Published: BMC 2017-08-01
Series:BMC Research Notes
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13104-017-2715-5
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author Kiyoshi Migita
Nozomi Iwanaga
Yasumori Izumi
Chieko Kawahara
Kenji Kumagai
Tadashi Nakamura
Tomohiro Koga
Atsushi Kawakami
author_facet Kiyoshi Migita
Nozomi Iwanaga
Yasumori Izumi
Chieko Kawahara
Kenji Kumagai
Tadashi Nakamura
Tomohiro Koga
Atsushi Kawakami
author_sort Kiyoshi Migita
collection DOAJ
description Abstract Background MicroRNAs (miRNAs) are important regulators of a variety of inflammatory mediators. The present study was undertaken to elucidate the role of miRNAs in the rheumatoid cytokine network. Methods We analyzed miRNA expression in rheumatoid synovial fibroblasts (RASFs). miRNA array-based screening was used to identify miRNAs differentially expressed between tumor necrosis factor-α (TNF-α)-activated RASFs and untreated RASFs. Transfection of RASFs with miR-155 was used to analyze the function of miR-155. Real-time polymerase chain reaction (PCR) was used to measure the levels of miR-155 in RASFs. Results miRNA microarray analysis revealed that miR-155-5p was the most highly induced miRNA in TNF-α-stimulated RASFs. TNF-α-induced miR-155 expression in RASFs was time-dependent and TNFα dose-dependent, whereas, IL-6 stimulation did not affect miR-155 expression in RASFs. Transfection of miR-155 mimics into RASFs resulted in the decrease JAK2/STAT3 phosphorylation in IL-6-treated RASFs. Conclusions The current results demonstrate that TNF-α modulated miRNA expressions in RASFs. Our data showed that miR-155, which is highly induced by TNF-α stimulation, inhibits IL-6-mediated JAK2/STAT3 activation in RASFs. These findings suggest that miR-155 contributes to the cross-regulation between TNF-α and IL-6-mediated inflammatory pathways in RA.
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spelling doaj.art-a654d95a84184e6a87571b70786e79df2022-12-22T03:36:03ZengBMCBMC Research Notes1756-05002017-08-011011610.1186/s13104-017-2715-5TNF-α-induced miR-155 regulates IL-6 signaling in rheumatoid synovial fibroblastsKiyoshi Migita0Nozomi Iwanaga1Yasumori Izumi2Chieko Kawahara3Kenji Kumagai4Tadashi Nakamura5Tomohiro Koga6Atsushi Kawakami7Department of Rheumatology, Fukushima Medical UniversityDepartment of Rheumatology and Clinical Research Center, NHO Nagasaki Medical CenterDepartment of Rheumatology and Clinical Research Center, NHO Nagasaki Medical CenterDepartment of Rheumatology and Clinical Research Center, NHO Nagasaki Medical CenterDepartment of Orthopedics, Clinical Research Center, NHO Nagasaki Medical CenterDepartment of Rheumatology, Shinto Kumamoto HospitalDepartment of Rheumatology, Nagasaki University Graduate School of Biomedical SciencesDepartment of Rheumatology, Nagasaki University Graduate School of Biomedical SciencesAbstract Background MicroRNAs (miRNAs) are important regulators of a variety of inflammatory mediators. The present study was undertaken to elucidate the role of miRNAs in the rheumatoid cytokine network. Methods We analyzed miRNA expression in rheumatoid synovial fibroblasts (RASFs). miRNA array-based screening was used to identify miRNAs differentially expressed between tumor necrosis factor-α (TNF-α)-activated RASFs and untreated RASFs. Transfection of RASFs with miR-155 was used to analyze the function of miR-155. Real-time polymerase chain reaction (PCR) was used to measure the levels of miR-155 in RASFs. Results miRNA microarray analysis revealed that miR-155-5p was the most highly induced miRNA in TNF-α-stimulated RASFs. TNF-α-induced miR-155 expression in RASFs was time-dependent and TNFα dose-dependent, whereas, IL-6 stimulation did not affect miR-155 expression in RASFs. Transfection of miR-155 mimics into RASFs resulted in the decrease JAK2/STAT3 phosphorylation in IL-6-treated RASFs. Conclusions The current results demonstrate that TNF-α modulated miRNA expressions in RASFs. Our data showed that miR-155, which is highly induced by TNF-α stimulation, inhibits IL-6-mediated JAK2/STAT3 activation in RASFs. These findings suggest that miR-155 contributes to the cross-regulation between TNF-α and IL-6-mediated inflammatory pathways in RA.http://link.springer.com/article/10.1186/s13104-017-2715-5CytokinesInterleukin-6MicroRNAsRheumatoid arthritisSynovial fibroblastsTumor necrosis factor-α
spellingShingle Kiyoshi Migita
Nozomi Iwanaga
Yasumori Izumi
Chieko Kawahara
Kenji Kumagai
Tadashi Nakamura
Tomohiro Koga
Atsushi Kawakami
TNF-α-induced miR-155 regulates IL-6 signaling in rheumatoid synovial fibroblasts
BMC Research Notes
Cytokines
Interleukin-6
MicroRNAs
Rheumatoid arthritis
Synovial fibroblasts
Tumor necrosis factor-α
title TNF-α-induced miR-155 regulates IL-6 signaling in rheumatoid synovial fibroblasts
title_full TNF-α-induced miR-155 regulates IL-6 signaling in rheumatoid synovial fibroblasts
title_fullStr TNF-α-induced miR-155 regulates IL-6 signaling in rheumatoid synovial fibroblasts
title_full_unstemmed TNF-α-induced miR-155 regulates IL-6 signaling in rheumatoid synovial fibroblasts
title_short TNF-α-induced miR-155 regulates IL-6 signaling in rheumatoid synovial fibroblasts
title_sort tnf α induced mir 155 regulates il 6 signaling in rheumatoid synovial fibroblasts
topic Cytokines
Interleukin-6
MicroRNAs
Rheumatoid arthritis
Synovial fibroblasts
Tumor necrosis factor-α
url http://link.springer.com/article/10.1186/s13104-017-2715-5
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