scholarly journals A MicroRNA93–Interferon Regulatory Factor-9–Immunoresponsive Gene-1–Itaconic Acid Pathway Modulates M2-Like Macrophage Polarization to Revascularize Ischemic Muscle

Circulation ◽  
2017 ◽  
Vol 135 (24) ◽  
pp. 2403-2425 ◽  
Author(s):  
Vijay Chaitanya Ganta ◽  
Min Hyub Choi ◽  
Anna Kutateladze ◽  
Todd E. Fox ◽  
Charles R. Farber ◽  
...  
Keyword(s):  
Itaconic Acid ◽  
Macrophage Polarization ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Acid Pathway ◽  
Ischemic Muscle

scholarly journals The COP9 Signalosome Interacts with and Regulates Interferon Regulatory Factor 5 Protein Stability

2012 ◽  
Vol 33 (6) ◽  
pp. 1124-1138 ◽  
Author(s):  
Justyna Korczeniewska ◽  
Betsy J. Barnes
Keyword(s):  
Protein Stability ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Death Receptor ◽  
Interferon Regulatory Factor ◽  
Cop9 Signalosome ◽  
Small Interfering Rnas ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 5 ◽  
Enhanced Degradation

The transcription factor interferon regulatory factor 5 (IRF5) exerts crucial functions in the regulation of host immunity against extracellular pathogens, DNA damage-induced apoptosis, death receptor signaling, and macrophage polarization. Tight regulation of IRF5 is thus warranted for an efficient response toward extracellular stressors and for limiting autoimmune and inflammatory responses. Here we report that the COP9 signalosome (CSN), a general modulator of diverse cellular and developmental processes, associates constitutively with IRF5 and promotes its protein stability. The constitutive CSN/IRF5 interaction was identified using proteomics and confirmed by endogenous immunoprecipitations. The CSN/IRF5 interaction occurred on the carboxyl and amino termini of IRF5; a single internal deletion from amino acids 455 to 466 (Δ455-466) was found to significantly reduce IRF5 protein stability. CSN subunit 3 (CSN3) was identified as a direct interacting partner of IRF5, and knockdown of this subunit with small interfering RNAs resulted in enhanced degradation. Degradation was further augmented by knockdown of CSN1 and CSN3 together. The ubiquitin E1 inhibitor UBEI-41 or the proteasome inhibitor MG132 prevented IRF5 degradation, supporting the idea that its stability is regulated by the ubiquitin-proteasome system. Importantly, activation of IRF5 by the death receptor ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resulted in enhanced degradation via loss of the CSN/IRF5 interaction. This study defines CSN to be a new interacting partner of IRF5 that controls its stability.

scholarly journals Polysaccharides from Citrus grandis associate with luteolin relieves chronic pharyngitis by anti-inflammatory via suppressing NF-κB pathway and the polarization of M1 macrophages

2018 ◽  
Vol 32 ◽  
pp. 205873841878059 ◽  
Author(s):  
Xiumei Chen ◽  
Yongfeng Lai ◽  
Xicheng Song ◽  
Jinying Wu ◽  
Li Wang ◽  
...  
Keyword(s):  
Disease Severity ◽  
Macrophage Polarization ◽  
Mannose Receptor ◽  
Interferon Regulatory Factor ◽  
Protective Effects ◽  
Regulatory Factor ◽  
Necrosis Factor Alpha ◽  
Ear Edema ◽  
M1 Macrophage ◽  
Anti Inflammatory

Chronic pharyngitis is characterized as a common inflammation of the pharyngeal mucosa, and anti-inflammatory medications are the common treatment to relieve it. Polysacharides of Citrus grandis L. Osbeck (PCG) and luteolin have been reported to have anti-inflammatory activities. In this study, the protective effects of PCG and luteolin on chronic pharyngitis are evaluated and the underlying mechanisms are explored. PCG and luteolin are administrated to animal models with granuloma, ear edema and chronic pharyngitis and the effects of PCG and luteolin on disease severity are evaluated. We also evaluate the effects of PCG and luteolin on inflammatory cytokine production in macrophages stimulated with lipopolysaccharides (LPS)/interferon-gamma (IFN-γ) and detect the effects of PCG and luteolin on macrophage polarization. Finally, we evaluate the effects of PCG and luteolin on activations of LPS-induced downstream signaling pathways. PCG and luteolin alleviate the disease severity of granuloma, ear edema and chronic pharyngitis. PCG and luteolin suppress the productions of pro-inflammatory cytokines interlukin-6 (IL-6), interlukin-12 (IL-12) and tumor necrosis factor alpha (TNF-α) in macrophages. Luteolin promotes macrophage M2 polarization by enhancing expressions of arginase (Arg1) and mannose receptor C type 1 (Mrc1). PCG and luteolin suppress nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and interferon regulatory factor 1 (IRF1), interferon regulatory factor 5 (IRF5) expression. PCG together with luteolin relieves chronic pharyngitis by anti-inflammatory via suppressing NF-κB pathway and the polarization of M1 macrophage.

M2C Polarization by Baicalin Enhances Efferocytosis via Upregulation of MERTK Receptor

2018 ◽  
Vol 46 (08) ◽  
pp. 1899-1914 ◽  
Author(s):  
Yin-Siew Lai ◽  
Renanda Baghaz Dzulhamdhani Surya Putra ◽  
Shin-Peir Aui ◽  
Ko-Tung Chang
Keyword(s):  
Macrophage Polarization ◽  
Chinese Herb ◽  
Interleukin 10 ◽  
Interferon Regulatory Factor ◽  
M2 Macrophage ◽  
Gene Transcript ◽  
Regulatory Factor ◽  
Necrosis Factor Alpha ◽  
Murine Bone Marrow ◽  
Arginase 1

Baicalin is the main active ingredient primary isolated from the Chinese herb, Scutellaria baicalensis Georgi. Although baicalin can induce M2 macrophage polarization, we still do not know the subtype of macrophages polarized by baicalin. In this study, we characterized that murine bone marrow derived macrophages induced by M-CSF can be further polarized into M2C phenotype by baicalin. The signatures of M2C macrophages for mRNA expression like interferon regulatory factor 4 (IRF4), interleukin-10 (IL-10), MERTK and PTX3 were up-regulated. Moreover, we observed the concomitantly decreasing of tumor necrosis factor alpha (TNF-[Formula: see text]), interferon regulatory factor 5 (IRF5), IL-6. In contrast, M2 macrophages polarized by IL-4 increased gene transcript of arginase-1 (Arg-1) and surface marker of CD206 indicates that their identity as M2A rather than M2C subtypes. Interestingly, the phagocytosis as well as efferocytosis activity were significantly enhanced in M2C macrophage polarized by baicalin and these capacities were associated with the expression of MERTK receptor. Finally, we conclude that baicalin induced M2C macrophages polarization with both elevations of efferocytosis and anti-inflammatory activity.

scholarly journals Increased Adipose Tissue Expression of Interferon Regulatory Factor (IRF)-5 in Obesity: Association with Metabolic Inflammation

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1418 ◽  
Author(s):  
Sardar Sindhu ◽  
Reeby Thomas ◽  
Shihab Kochumon ◽  
Ajit Wilson ◽  
Mohamed Abu-Farha ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Protein Expression ◽  
Macrophage Polarization ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Metabolic Inflammation ◽  
M1 Macrophage ◽  
Gene And Protein Expression ◽  
Local Expression

Interferon regulatory factor (IRF)-5 is known to be involved in M1 macrophage polarization, however, changes in the adipose expression of IRF5 in obesity and their relationship with the local expression of proinflammatory cytokines/chemokines are unknown. Therefore, IRF5 gene expression was determined in the subcutaneous adipose tissue samples from 53 non-diabetic individuals (6 lean, 18 overweight, and 29 obese), using real-time RT-PCR. IRF5 protein expression was also assessed using immunohistochemistry and/or confocal microscopy. Adipose gene expression of signature immune metabolic markers was also determined and compared with adipose IRF5 gene expression. Systemic levels of C-reactive protein and adiponectin were measured by ELISA. The data show that adipose IRF5 gene (P = 0.008) and protein (P = 0.004) expression was upregulated in obese compared with lean individuals. IRF5 expression changes correlated positively with body mass index (BMI; r = 0.37/P = 0.008) and body fat percentage (r = 0.51/P = 0.0004). In obese, IRF5 changes associated positively with HbA1c (r = 0.41/P = 0.02). A good agreement was found between gene and protein expression of IRF5 in obese subjects (r = 0.65/P = 0.001). IRF5 gene expression associated positively with adipose inflammatory signatures including local expression of TNF-α, IL-6, CXCL8, CCL-2/5, IL-1β, IL-18, CXCL-9/10, CCL7, CCR-1/2/5, TLR-2/7/8/9, IRF3, MyD88, IRAK-1, and inflammatory macrophage markers (P < 0.05). Interestingly, IRF5 gene expression correlated positively with CRP (r = 0.37, P = 0.03) and negatively with adiponectin levels (r = −0.43, P = 0.009). In conclusion, elevated adipose IRF5 expression in obesity concurs with the typical inflammatory signatures, locally and systemically. Hence, the IRF5 upregulation may represent a novel adipose tissue marker for metabolic inflammation.

scholarly journals The interferon regulatory factor IRF5 is differentially expressed in the blood of patients with viral co-infections.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Influenza A ◽  
Macrophage Polarization ◽  
Cell Lineage ◽  
Interferon Regulatory Factor ◽  
Human Rhinovirus ◽  
Differentially Expressed ◽  
Influenza B ◽  
Regulatory Factor ◽  
Transcriptional Responses ◽  
Human Coronavirus

Co-infection is a process by which the same host can be infected with two pathogens. By mining published microarray data (1), we found that the gene encoding the interferon regulatory factor 5 (IRF5) was among the genes most differentially expressed in the blood of seven patients with viral co-infections: in one patient with human coronavirus OC43 and Influenza A co-infection, in one patient with human coronavirus NL63 and Human Rhinovirus co-infection, and in five patients with Influenza B and Human Rhinovirus co-infection. IRF5 has described functions in macrophage polarization, T-cell lineage specification (2), B-cell development (3), innate immune signal transduction (4) and in transcriptional responses to viral infection (5), and could potentially be relevant to processes underlying viral co-infection.

scholarly journals Corrected and Republished from: The COP9 Signalosome Interacts with and Regulates Interferon Regulatory Factor 5 Protein Stability

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Justyna Korczeniewska ◽  
Betsy J. Barnes
Keyword(s):  
Protein Stability ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Death Receptor ◽  
Interferon Regulatory Factor ◽  
Cop9 Signalosome ◽  
Small Interfering Rnas ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 5 ◽  
Enhanced Degradation

ABSTRACT The transcription factor interferon regulatory factor 5 (IRF5) exerts crucial functions in the regulation of host immunity against extracellular pathogens, DNA damage-induced apoptosis, death receptor signaling, and macrophage polarization. Tight regulation of IRF5 is thus warranted for an efficient response to extracellular stressors and for limiting autoimmune and inflammatory responses. Here we report that the COP9 signalosome (CSN), a general modulator of diverse cellular and developmental processes, associates constitutively with IRF5 and promotes its protein stability. The constitutive CSN/IRF5 interaction was identified using proteomics and confirmed by endogenous immunoprecipitations. The CSN/IRF5 interaction occurred on the carboxyl and amino termini of IRF5; a single internal deletion (Δ455-466) was found to significantly reduce IRF5 protein stability. CSN3 was identified as a direct interacting partner of IRF5, and knockdown of this subunit with small interfering RNAs (siRNAs) resulted in enhanced degradation. Degradation was further augmented by knockdown of CSN1 and CSN3 together. The ubiquitin E1 inhibitor UBEI-41 or the proteasome inhibitor MG132 prevented IRF5 degradation, supporting that its stability is regulated by the ubiquitin-proteasome system. Importantly, activation of IRF5 by the death receptor ligand tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) resulted in enhanced degradation via loss of the CSN/IRF5 interaction. This study defines the CSN as a new interacting partner of IRF5 that controls its stability.

Sign in / Sign up

Export Citation Format

Share Document