Immunoregulatory Role of MicroRNA-21 in Macrophages in Response to Bacillus Calmette-Guerin Infection Involves Modulation of the TLR4/MyD88 Signaling Pathway

Background/Aims: The purpose of this study is to explore the immunoregulatory role of microRNA-21 (miR-21) targeting of the TLR4/MyD88 signaling pathway in macrophages in response to Bacillus Calmette-Guerin (BCG) infection. Methods: After infection with BCG, mouse RAW246.7 cells were assigned into...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Cellular physiology and biochemistry Jg. 42; H. 1; S. 91 - 102
Hauptverfasser: Xue, Xin, Qiu, Yi, Yang, Hong-Li
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Basel, Switzerland S. Karger AG 01.01.2017
Cell Physiol Biochem Press GmbH & Co KG
Schlagworte:
Animals
Antagomirs - metabolism
Apoptosis
Bacilli Calmette-Guerin
Base Sequence
Biological products
Cancer
Cardiovascular disease
Enzyme-Linked Immunosorbent Assay
Gene expression
Infections
Interleukin-10 - analysis
Interleukin-6 - analysis
Laboratories
Leukemia
Macrophage
Mice
MicroRNA-21
MicroRNAs
MicroRNAs - antagonists & inhibitors
MicroRNAs - genetics
MicroRNAs - metabolism
Microscopy, Electron, Transmission
Mycobacterium bovis - physiology
Myeloid differentiation factor 88
Myeloid Differentiation Factor 88 - genetics
Myeloid Differentiation Factor 88 - metabolism
Pathogens
Proteins
RAW 264.7 Cells
Retracted Paper
RNA, Messenger - metabolism
Sequence Alignment
Signal Transduction - drug effects
Signaling pathway
Stem cells
Sulfonamides - pharmacology
Toll-Like Receptor 4 - antagonists & inhibitors
Toll-Like Receptor 4 - genetics
Toll-Like Receptor 4 - metabolism
Toll-like receptors 4
Tuberculosis
Tumor Necrosis Factor-alpha - analysis
United States > US
China
Utah
Myeloid differentiation factor 88
MicroRNA-21
Signaling pathway
Toll-like receptors 4
Bacilli Calmette-Guerin
Macrophage
ISSN:1015-8987, 1421-9778, 1421-9778
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Background/Aims: The purpose of this study is to explore the immunoregulatory role of microRNA-21 (miR-21) targeting of the TLR4/MyD88 signaling pathway in macrophages in response to Bacillus Calmette-Guerin (BCG) infection. Methods: After infection with BCG, mouse RAW246.7 cells were assigned into control, BCG, miR-21 mimic + BCG, mimic-negative control (NC) + BCG, miR-21 inhibitor + BCG, inhibitor-NC + BCG, BCG + TAK242 (an inhibitor of the TLR4 signaling pathway), and miR-21 inhibitor + TAK242 + BCG groups. Western blotting and qRT-PCR were used to detect the expression of miR-21, TLR4 and MyD88. The levels of TNF-a, IL-6 and IL-10 were detected by enzyme-linked immunosorbent assay (ELISA). Cell viability was measured using an MTT assay. Cell apoptosis and necrosis rates were detected using flow cytometry. Results: Compared with the control group, miR-21 expression and levels of TNF-a, IL-6 and IL-10, as well as cell apoptosis and necrosis rates, were elevated, while expression of TLR4 and MyD88, as well as cell viability, were reduced in BCG infection groups. Compared with the BCG group, miR-21 expression was increased in the miR-21 mimic + BCG group but decreased in the miR-21 inhibitor + BCG and miR-21 inhibitor + TAK242 + BCG groups. The expression of TLR4 and MyD88, as well as the cell viability, were decreased, while levels of TNF-a, IL-6 and IL-10, as well as cell apoptosis and necrosis rates, were increased in the miR-21 mimic + BCG and TAK242 + BCG groups. The opposite trends were found in the miR-21 inhibitor + BCG group. Compared with the TAK242 + BCG group, the miR-21 inhibitor + TAK242 + BCG group had higher expression of TLR4 and MyD88 as well as higher cell viability and lower levels of TNF-a, IL-6, IL-10, cell apoptosis and necrosis rates. However, the miR-21 inhibitor + TAK242 + BCG group exhibited the opposite trends when compared with the miR-21 inhibitor + BCG group. Conclusion: Our results suggest that miR-21 can negatively modulate the TLR4/MyD88 signaling pathway, resulting in decreased cell viability, increased cell apoptosis and increased levels of inflammatory factors following BCG infection in macrophages.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ObjectType-Correction/Retraction-3
ISSN:1015-8987
1421-9778
1421-9778
DOI:10.1159/000477118