Mint3/Apba3 depletion ameliorates severe murine influenza pneumonia and macrophage cytokine production in response to the influenza virus

MDA5 belongs to the RIG-I-like receptor family, which is involved in innate immunity. During viral infection, MDA5 generates an antiviral response by recognizing the ligand to activate interferon. However, the role and mechanism of MDA5 in canine influenza virus (CIV) infection are unclear. To understand the mechanism of canine MDA5-mediated innate immunity during CIV infection, we detected the distribution of MDA5 in beagles, and the structural prediction showed that MDA5 was mainly composed of a CARD domain, RD domain, and DExD/H helix structure. Moreover, we found that MDA5 inhibits CIV replication. Furthermore, in the dual luciferase assay, we revealed that the CARD region of MDA5 strongly activated the IFN-β promoter and mainly transmitted signals through the CARD region. Overexpression of the CARD region of MDA5 revealed that the MDA5-mediated signaling pathway could transmit signals by activating the IRF3/NF-κB and IRF3 promoters, promoting the expression of antiviral proteins and cytokine release, thereby inhibiting CIV replication. Upon silencing of MDA5, cytokine production decreased, while the replication ability of CIV was increased. Thus, this study revealed a novel mechanism by which MDA5 mediated CIV infection and provided new avenues for the development of antiviral strategies.

Download Full-text

A Simple Glycolipid Mimic of the Phosphatidylinositol Mannoside Core from Mycobacterium tuberculosis Inhibits Macrophage Cytokine Production

ChemBioChem ◽

10.1002/cbic.201800150 ◽

2018 ◽

Vol 19 (14) ◽

pp. 1476-1481 ◽

Cited By ~ 3

Author(s):

Tamim Mosaiab ◽

Sandra Boiteux ◽

Abu Hasanat Md Zulfiker ◽

Ming Q. Wei ◽

Milton J. Kiefel ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Cytokine Production ◽

Macrophage Cytokine

Download Full-text

Evaluation of Murine Macrophage Cytokine Production After In Vivo Morphine Treatment

Methods in Molecular Biology - Opioid Receptors ◽

10.1007/978-1-4939-1708-2_21 ◽

2014 ◽

pp. 253-261 ◽

Cited By ~ 1

Author(s):

Silvia Franchi ◽

Mara Castelli ◽

Sarah Moretti ◽

Alberto Panerai ◽

Paola Sacerdote

Keyword(s):

Cytokine Production ◽

Murine Macrophage ◽

Morphine Treatment ◽

Macrophage Cytokine

Download Full-text

Cyclosporin A Decreases Human Macrophage Interleukin-6 Synthesis at Post-Transcriptional Level

Mediators of Inflammation ◽

10.1080/09629359990423 ◽

1999 ◽

Vol 8 (4-5) ◽

pp. 253-259 ◽

Cited By ~ 17

Author(s):

Juan E. Losa García ◽

Ana M. Rodríguez López ◽

María Rosa Martín De Cabo ◽

Fernando Mateos Rodríguez ◽

Jesús Pérez Losada ◽

...

Keyword(s):

Cyclosporin A ◽

Interleukin 6 ◽

Cytokine Production ◽

Regulatory Protein ◽

Inhibition Mechanism ◽

Transcriptional Level ◽

Mrna Levels ◽

Cytokine Inhibition ◽

Cytokine Synthesis ◽

Macrophage Cytokine

In addition to its well-established effect on T cells, cyclosporin A (CsA) also inhibits inflammatory cytokine production by macrophages. However, little is known about the mechanism of action of CsA on macrophage cytokine production. We measured the effect of CsA on basal and phorbol-myristate-acetate (PMA)-stimulated production of interleukin-6 using the human monocyte cell line U937 differentiated with dimethylsulfoxide (DMSO). Interleukin-6 levels were measured in supernatant and cell lysates using specific enzyme-linked immunosorbent assays. We found that CsA decreases not only IL-6 release but also cytokine synthesis. The concentration of CsA used did not affect either cell viability or proliferation. Three possibilities may be advanced to explain the CsA-due decrease in IL-6 production by macrophages: (a) inhibition of the synthesis of an early common regulatory protein, (b) inhibition of cytokine gene transcription, or (c) modulation of post-transcriptional events. The first possibility was tested by measuring the effect of cycloheximide on the experimental system during the first 3 hours of culture. Although cycloheximide decreased total cytokine synthesis, the pattern of cytokine modulation by CsA persisted. These data suggest that CsA-mediated macrophage cytokine inhibition is not mediated by an early common regulatory protein. To further explore the inhibition mechanism, we measured IL-6 mRNA levels by Northern blot. IL-6 mRNA levels were unaffected by CsA both in resting and PMA-stimulated cells. We conclude that in human macrophages CsA diminishes IL-6 production at post-transcriptional level.

Download Full-text

Inhibition of primary murine macrophage cytokine production in vitro following treatment with the K-opioid agonist U50, 488H

Journal of Neuroimmunology ◽

10.1016/0165-5728(95)00159-x ◽

1996 ◽

Vol 64 (1) ◽

pp. 83-90 ◽

Cited By ~ 66

Author(s):

Candido Alicea ◽

Stanley Belkowski ◽

Toby K. Eisenstein ◽

Martin W. Adler ◽

Thomas J. Rogers

Keyword(s):

Cytokine Production ◽

Murine Macrophage ◽

Opioid Agonist ◽

Macrophage Cytokine

Download Full-text

Systemic Inflammation Induced by microRNAs: Endometriosis-Derived Alterations in Circulating microRNA 125b-5p and Let-7b-5p Regulate Macrophage Cytokine Production

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2017-01199 ◽

2017 ◽

Vol 103 (1) ◽

pp. 64-74 ◽

Cited By ~ 23

Author(s):

Sepide E Nematian ◽

Ramanaiah Mamillapalli ◽

Trisha S Kadakia ◽

Masoumeh Majidi Zolbin ◽

Sarah Moustafa ◽

...

Keyword(s):

Messenger Rna ◽

Cytokine Production ◽

University Hospital ◽

Regulatory Function ◽

Enzyme Linked Immunosorbent Assay ◽

Circulating Microrna ◽

Protein Levels ◽

Tnf Α ◽

Factor Α ◽

Macrophage Cytokine

Abstract Context Endometriosis is characterized by aberrant inflammation. We previously reported increased levels of microRNA (miRNA) 125b-5p and decreased levels of miRNA Let-7b-5p in serum of patients with endometriosis. Objective Determine the regulatory function of miRNAs 125b-5p and Let-7b-5p on production of proinflammatory cytokines in endometriosis. Design Case-control study. Setting University hospital. Patients Women with (20) and without (26) endometriosis; human U937 macrophage cell line. Intervention Sera were collected from surgically diagnosed patients and differentiated U937 cells that were transfected with miRNAs 125b-5p and Let-7b-5p mimics and inhibitor. Main Outcome Measures Enzyme-linked immunosorbent assay for tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and IL-1β levels and quantitative real-time polymerase chain reaction for expression of miRNAs 125b-5p and Let-7b-5p in sera of patients with and without endometriosis. Transfected macrophages were evaluated for expression of inflammatory cytokines, intracellular production, and secretion of these cytokines. Results We noted substantial elevation of TNF-α, IL-1β, and IL-6, marked upregulation of miRNA 125b, and considerable downregulation of Let-7b in sera of patients with endometriosis vs control. There was a positive correlation between miRNA 125b levels and TNF-α, IL-1β, and IL-6 and a negative correlation between miRNA Let-7b levels and TNF-α in sera of patients with endometriosis. Transfection experiments showed a noteworthy upregulation of TNF-α, IL-1β, IL-6, and IL-8 in macrophages transfected with miRNA 125b mimic or Let-7b inhibitor. The secreted cytokine protein levels and intracellular imaging studies closely correlate with the messenger RNA changes. Conclusions Endometriosis-derived miRNAs regulate macrophage cytokine production that contributes to inflammation associated with this condition.

Download Full-text