IRF-3

To compare the effectiveness of different types of high-intensity interval training (HIIT) on meta-inflammation during obesity, TLR4 pathway activities were assessed following a 10-week randomized trial. 30 young females with overweight and obesity were randomly allocated to aerobic HIIT (HIIT/AE) or resistance exercise in HIIT (HIIT/RE) and performed a 28-minute (4 × 4 min) in each session. During each interval, the HIIT/AE performed four minutes of all-extremity cycling, whereas the HIIT/RE completed four minutes of combined resistance exercises and all-extremity cycling...

Radiation-induced brain injury (RIBI) is one of the most common and fatal complications of cranial radiation therapy (CRT); however, no effective intervention is available currently. Metformin has been reported to have anti-RIBI activity as a first-line anti-diabetic drug. However, the mechanism of action is unclear. An RIBI mice model and an in vitro cell model under 30 and 10 Gy 60 Co γ-rays exposure were established to investigate the mechanism of metformin in RIBI. The results showed that pre-treatment with metformin protects hippocampal neurogenesis in the brain of mice and improves learning and memory ability after irradiation...

Interferon (IFN), the most effective antiviral cytokine, is involved in innate and adaptive immune responses and is essential to the host defense against virus invasion. Once the host was infected by pathogens, the pathogen-associated molecular patterns (PAMPs) were recognized by the host pattern recognition receptors (PRRs), which activates interferon regulatory transcription factors (IRFs) and nuclear factor-kappa B (NF-κB) signal transduction pathway to induce IFN expression. Pathogens have acquired many strategies to escape the IFN-mediated antiviral immune response...

Production of nitric oxide (NO) by LPS-activated macrophages is due to a complex cellular signaling initiated by TLR4 that leads to the transcription of IFN-β, which activates IRF-1 and STAT-1, as well as to the activation of NF-κB, required for iNOS transcription. High concentrations of LPS can also be uptaken by scavenger receptors (SRs), which, in concert with TLR4, leads to inflammatory responses. The mechanisms by which TLR4 and SRs interact, and the pathways activated by this interaction in macrophages are not elucidated...

TNF receptor-associated factor 6 (TRAF6) plays a key signal transduction role in both antibacterial and antiviral signaling pathways. However, the regulatory mechanisms of TRAF6 in lower vertebrates are less reported. In this study, we identify calpain2a, is a member of the calcium-dependent proteases family with unique hydrolytic enzyme activity, functions as a key regulator for antibacterial and antiviral immunity in teleost fish. Upon lipopolysaccharide (LPS) stimulation, knockdown of calpain2a promotes the upregulation of inflammatory cytokines...

The objective of this study was to generate small interfering RNA (siRNA) to knockdown antiviral chemokine-related genes in fetal rhesus monkey kidney (FRhK-4) cells. We generated siRNA duplexes to suppress antiviral chemokines like CXCL10 and CCL4 in FRhK-4 cells by downregulating interferon regulatory factor (IRF) 3 and IRF7. Three siRNA duplexes (si-F-IRF3-1, si-F-IRF3-2, and si-F-IRF3-3) targeting IRF3, and one siRNA duplex (si-F-IRF7) targeting IRF7 were generated. A nontarget siRNA duplex was used as the negative control...

It is recognized that the cerebral ischemia/reperfusion (I/R) injury triggers inflammatory activation of microglia and supports microglia-driven neuronal damage. Our previous studies have shown that ginsenoside Rg1 had a significant protective effect on focal cerebral I/R injury in middle cerebral artery occlusion (MCAO) rats. However, the mechanism still needs further clarification. Here, we firstly reported that ginsenoside Rg1 effectively suppressed the inflammatory activation of brain microglia cells under I/R conditions depending on the inhibition of Toll-likereceptor4 (TLR4) proteins...

Sepsis-associated acute kidney injury (S-AKI) is a frequent complication in critically ill patients, which is often initiated by glomerular endothelial cell dysfunction. Although transient receptor vanilloid subtype 4 (TRPV4) ion channels are known to be permeable to Ca2+ and widely expressed in kidneys, the role of TRPV4 on glomerular endothelial inflammation in sepsis remains elusive. In the present study, we found that TRPV4 expression in mouse glomerular endothelial cells (MGECs) increased after lipopolysaccharide (LPS) stimulation or cecal ligation and puncture (CLP) challenge, which increased intracellular Ca2+ in MGECs...

Multiple sclerosis (MS) is a chronic disease and one of the leading causes of disability in young adults. The current study aims to investigate the pathogenesis of MS via studying the regulatory role of novel lncRNA MAGI2-AS3 in miR-374b-5p and their downstream targets PTEN/AKT/IRF-3/IFN-β and the relationship of this pathway with disease severity. Moreover, it aims to assess the role of MAGI2-AS3/miR-374b-5p as diagnostic and/or prognostic biomarkers for MS. Overall, 150 contributors were recruited: 100 patients with MS and 50 healthy volunteers...

Obesity is increasing in incidence worldwide, especially in women, which can affect the outcome of pregnancy. During this period, viral infections represent a risk to the mother, the placental unit, and the fetus. The Zika virus (ZIKV) outbreak in Brazil has been the cause of congenital Zika syndrome (CZS), with devastating consequences such as microcephaly in newborns. Herein, we analyzed the impact of maternal overweight/obesity on the antiviral factors' expression in the placental tissue of Zika-infected mothers...

We disclose here a panel of small-molecule TLR4 agonists (the FP20 series) whose structure is derived from previously developed TLR4 ligands ( FP18 series). The new molecules have increased chemical stability and a shorter, more efficient, and scalable synthesis. The FP20 series showed selective activity as TLR4 agonists with a potency similar to FP18 . Interestingly, despite the chemical similarity with the FP18 series, FP20 showed a different mechanism of action and immunofluorescence microscopy showed no NF-κB nor p-IRF-3 nuclear translocation but rather MAPK and NLRP3-dependent inflammasome activation...

Prolonged interferon (IFN) signaling in cancer cells can promote resistance to immune checkpoint blockade (ICB). How cancer cells retain effects of prolonged IFN stimulation to coordinate resistance is unclear. We show that, across human and/or mouse tumors, immune dysfunction is associated with cancer cells acquiring epigenetic features of inflammatory memory. Here, inflammatory memory domains, many of which are initiated by chronic IFN-γ, are maintained by signal transducer and activator of transcription (STAT)1 and IFN regulatory factor (IRF)3 and link histone 3 lysine 4 monomethylation (H3K4me1)-marked chromatin accessibility to increased expression of a subset of IFN-stimulated genes (ISGs)...

To evaluate the effects of melatonin (MEL) on the expression of toll-like receptor-4 (TLR4); myeloid differentiation primary response protein-88 (MyD88); TIR-domain-containing adapter-inducing interferon-β (TRIF); IFN regulatory-factor-3 (IRF-3); nuclear factor kappa-B (NF-κB); plasma concentrations of interleukin-1β (IL-1β) and lipopolysaccharide (LPS); and lipid profile of rats with apical periodontitis (AP) fed on a high-fat diet (HFD). Eighty 60-day-old rats were divided into eight groups: control, AP, HFD, HFDAP, CNMEL, APMEL, HFDMEL and HFDAPMEL...

Steroid receptor RNA activator gene (SRA1) emerges as a player in pathophysiological responses of adipose tissue (AT) in metabolic disorders such as obesity and type 2 diabetes (T2D). We previously showed association of the AT SRA1 expression with inflammatory cytokines/chemokines involved in metabolic derangement. However, the relationship between altered adipose expression of SRA1 and the innate immune Toll-like receptors (TLRs) as players in nutrient sensing and metabolic inflammation as well as their downstream signaling partners, including interferon regulatory factors (IRFs), remains elusive...

Recent studies have shown a close link between viral infections and cholesterol metabolism. Here, we reported that 7-dehydrocholesterol reductase (DHCR7), a terminal enzyme for catalyzing cholesterol synthesis in the Kandutsch-Russell pathway, is harnessed by enterovirus A71 (EV-A71) benefitting for its replication. Overexpression of DHCR7 resulted in upregulating of EV-A71 replication, while the S14A mutation, which reduces DHCR7 enzyme activity, has no effect on EV-A71 replication. Knockdown of DHCR7 expression with small interfering RNA (siRNA) or enzyme activity inhibition with pharmacological inhibitor AY9944 could significantly inhibit EV-A71 replication...

Small GTPases play critical roles in cell morphology, movement, and adhesion by dynamic regulation of actin cytoskeleton. The small Rho GTPase Rif/RhoF (Rho in filopodia) regulates the formation of filopodia and stress fibers in cells. Rif is highly expressed in a number of cell types in the immune system; however, it's role in immune system function is unclear. In this research, we found that Rif expression is necessary for NF-κB activation in primary immune cells, and mature dendritic cell (mature DCs) induced from Bone Marrow-Derived Dendritic Cells (BMDCs) isolated from Rif knock out (Rif KO) mice displayed impaired degradation of I-κBα, as well as reduced TNF-α secretion and p38 MAPK phosphorylation under LPS stimulation...

Aims: The primary aim of the current study was to elucidate the function of the stimulator of interferon genes (STING) in the eutopic endometrium of women with endometriosis. Materials and Methods : STING expression and signaling pathways were verified by western blot analysis and immunohistochemistry after si-STING treatment. Cell proliferation and invasion and migration were assessed using 5-ethynyl-2'-deoxyuridine and transwell assays, respectively. Results : Within endometriosis tissues, STING was primarily expressed in the stroma of the eutopic endometrium and glandular epithelium of the ectopic endometrium...

Transcription factors related to the activation of type I interferons (IFNs) and nuclear factor-kappa B (NF-κB) are known to be critical in innate immune responses. Interferon regulatory factors (IRFs) are a family of transcription factors. IRF-3 is known to act as the primary regulator in type I IFN signaling in response to viral infections, and the upregulation of IRF5 by virus infection has been reported in various fish species. One of the ways to know the functional role of certain genes is the production of target gene(s) knockout cells or organisms...

Interferon regulatory factor (IRF) 3 and IRF7 are master regulators of type I interferon (IFN-I)-dependent antiviral innate immunity. Upon viral infection, a positive feedback loop is formed, wherein IRF7 promotes further induction of IFN-I in the later stage. Thus, it is critical to maintain a suitably low level of IRF7 to avoid the hyperproduction of IFN-I. In this study, we find that early expression of IFN-I-dependent STAT1 promotes the expression of XAF1 and that XAF1 is associated specifically with IRF7 and inhibits the activity of XIAP...

Tick-borne encephalitis virus (TBEV) is an important human arthropod-borne virus that causes tick-borne encephalitis (TBE) in humans. TBEV acutely infects the central nervous system (CNS), leading to neurological symptoms of various severity. No therapeutics are currently available for TBEV-associated disease. Virus strains of various pathogenicity have been described, although the basis of their diverse clinical outcome remains undefined. Work with infectious TBEV requires high-level biocontainment, meaning model systems that can recapitulate the virus life cycle are highly sought...