MicroRNA-204-3p inhibits lipopolysaccharide-induced cytokines in familial Mediterranean fever via the phosphoinositide 3-kinase γ pathway
Objective: We sought to identify the microRNA (miRNA) profile and potential biomarkers in FMF and to clarify their gene targets to elucidate the pathogenesis of FMF.
Methods: We performed an miRNA microarray using serum from FMF patients in attack and in remission. We then examined the expression of miRNAs in macrophages derived from THP-1 cells stimulated with toll-like receptor (TLR) ligands. Macrophages derived from THP-1 cells transfected with pre-miRNA were stimulated with lipopolysaccharides (LPSs) for the quantification of inflammatory cytokine production. To identify the target genes, we overexpressed their miRNA and performed a complementary DNA microarray. Transfection with reporter construct and the precursor miRNA was performed to confirm the suppression of target mRNA.
Results: We found that miR-204-3p was greatly decreased in the serum from FMF patients in attack. The expression of miR-204-3p was suppressed by LPS stimulation in the macrophages derived from THP-1 cells and the inhibition of miR-204-3p significantly induced the production of TLR4-related cytokines. The bioinformatic analysis showed that miR-204-3p is predicted to target genes implicated in the TLR pathway through the regulation of PI3Kγ signalling. The reporter assay revealed that miR-204-3p directly suppressed the luciferase activity of 3'-UTR of PIK3CG reporter construct. The inhibition of PI3Kγ resulted in decreased amounts of IL-6 and IL-12p40 in monocytes from FMF patients.
Conclusion: These data suggest that serum miR-204-3p has potential as a useful biomarker in FMF patients and that miR-204-3p serves as a suppressor of inflammatory cytokine production in FMF by targeting the PI3Kγ pathway.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:57 |
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| Enthalten in: |
Rheumatology (Oxford, England) - 57(2018), 4 vom: 01. Apr., Seite 718-726 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Koga, Tomohiro [VerfasserIn] |
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| Links: |
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| Themen: |
63231-63-0 |
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| Anmerkungen: |
Date Completed 25.05.2018 Date Revised 10.12.2019 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/rheumatology/kex451 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM279573847 |
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| 100 | 1 | |a Koga, Tomohiro |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a MicroRNA-204-3p inhibits lipopolysaccharide-induced cytokines in familial Mediterranean fever via the phosphoinositide 3-kinase γ pathway |
| 264 | 1 | |c 2018 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 25.05.2018 | ||
| 500 | |a Date Revised 10.12.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Objective: We sought to identify the microRNA (miRNA) profile and potential biomarkers in FMF and to clarify their gene targets to elucidate the pathogenesis of FMF | ||
| 520 | |a Methods: We performed an miRNA microarray using serum from FMF patients in attack and in remission. We then examined the expression of miRNAs in macrophages derived from THP-1 cells stimulated with toll-like receptor (TLR) ligands. Macrophages derived from THP-1 cells transfected with pre-miRNA were stimulated with lipopolysaccharides (LPSs) for the quantification of inflammatory cytokine production. To identify the target genes, we overexpressed their miRNA and performed a complementary DNA microarray. Transfection with reporter construct and the precursor miRNA was performed to confirm the suppression of target mRNA | ||
| 520 | |a Results: We found that miR-204-3p was greatly decreased in the serum from FMF patients in attack. The expression of miR-204-3p was suppressed by LPS stimulation in the macrophages derived from THP-1 cells and the inhibition of miR-204-3p significantly induced the production of TLR4-related cytokines. The bioinformatic analysis showed that miR-204-3p is predicted to target genes implicated in the TLR pathway through the regulation of PI3Kγ signalling. The reporter assay revealed that miR-204-3p directly suppressed the luciferase activity of 3'-UTR of PIK3CG reporter construct. The inhibition of PI3Kγ resulted in decreased amounts of IL-6 and IL-12p40 in monocytes from FMF patients | ||
| 520 | |a Conclusion: These data suggest that serum miR-204-3p has potential as a useful biomarker in FMF patients and that miR-204-3p serves as a suppressor of inflammatory cytokine production in FMF by targeting the PI3Kγ pathway | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a Lipopolysaccharides |2 NLM | |
| 650 | 7 | |a MIRN204 microRNA, human |2 NLM | |
| 650 | 7 | |a MicroRNAs |2 NLM | |
| 650 | 7 | |a Phosphoinositide-3 Kinase Inhibitors |2 NLM | |
| 650 | 7 | |a RNA |2 NLM | |
| 650 | 7 | |a 63231-63-0 |2 NLM | |
| 700 | 1 | |a Migita, Kiyoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Sato, Tomohito |e verfasserin |4 aut | |
| 700 | 1 | |a Sato, Shuntaro |e verfasserin |4 aut | |
| 700 | 1 | |a Umeda, Masataka |e verfasserin |4 aut | |
| 700 | 1 | |a Nonaka, Fumiaki |e verfasserin |4 aut | |
| 700 | 1 | |a Fukui, Shoichi |e verfasserin |4 aut | |
| 700 | 1 | |a Kawashiri, Shin-Ya |e verfasserin |4 aut | |
| 700 | 1 | |a Iwamoto, Naoki |e verfasserin |4 aut | |
| 700 | 1 | |a Ichinose, Kunihiro |e verfasserin |4 aut | |
| 700 | 1 | |a Tamai, Mami |e verfasserin |4 aut | |
| 700 | 1 | |a Nakamura, Hideki |e verfasserin |4 aut | |
| 700 | 1 | |a Origuchi, Tomoki |e verfasserin |4 aut | |
| 700 | 1 | |a Ueki, Yukitaka |e verfasserin |4 aut | |
| 700 | 1 | |a Masumoto, Junya |e verfasserin |4 aut | |
| 700 | 1 | |a Agematsu, Kazunaga |e verfasserin |4 aut | |
| 700 | 1 | |a Yachie, Akihiro |e verfasserin |4 aut | |
| 700 | 1 | |a Yoshiura, Koh-Ichiro |e verfasserin |4 aut | |
| 700 | 1 | |a Eguchi, Katsumi |e verfasserin |4 aut | |
| 700 | 1 | |a Kawakami, Atsushi |e verfasserin |4 aut | |
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