Background[1][2][3][4][5]
Phospho-IRF3(Ser386) Rabbit Monoclonal Antibody (phosphorylated interferon regulatory factor 3 rabbit monoclonal antibody) is used to systematically immunize rabbits with phosphorylated interferon regulatory factor 3 and then screen out rabbit phosphorylated interferon regulatory factor 3 After sensitizing B cells, they are hybridized with bone marrow tumor cells to finally produce a hybrid cell line that can produce a single antibody and proliferate indefinitely. Interferon regulatory factor 3, also known as IRF3, is an interferon regulatory factor. IRF3 is a member of the interferon-regulated transcription factor (IRF) family. IRF3 was originally discovered as a homolog of IRF1 and IRF2. IRF3 has been further characterized and shown to contain several functional domains, including a nuclear export signal, a DNA binding domain, a C-terminal IRF binding domain and several regulatory phosphorylation sites.
IRF3 exists in an inactive cytoplasmic form and is phosphorylated on serine/threonine to form a complex with CREBBP. This complex translocates into the nucleus and activates the transcription of interferon alpha and beta, as well as other interferon-induced genes. IRF3 plays an important role in the innate immune system’s response to viral infection. Aggregated MAVS has been found to activate IRF3 dimerization.
A recent study shows that phosphorylation of the innate immune adapter proteins MAVS, STING, and TRIF on the conserved pLxIS motif recruits and specifies IRF3 phosphorylation and activation of the serine/threonine protein kinase TBK1, thereby Limits the production of type I interferons. Another study showed that IRF3-/- knockout protects against myocardial infarction. The same study identified IRF3 and type I IFN responses as potential therapeutic targets for cardioprotection after myocardial infarction.
Research Application[6]
Phospho-IRF3(Ser386)Rabbit Monoclonal Antibody can be used to study the mechanism by which LXRα negatively regulates LPS-induced inflammatory response in Kupffer cells by downregulating IRF3 and GRIP1.
Methods: The expression of interferon regulatory factor 3 (IRF3), glucocorticoid receptor responsive protein 1 (GRIP1) and LXRα in Kupffer cells after lipopolysaccharide (LPS) stimulation with liver X receptor α (LXRα) agonist was observed. The effect of LXRα is to explore the related mechanism of LXRα negatively regulating inflammatory response. Methods Kupffer cells from the liver of male KM mice were isolated and cultured using collagenase in situ perfusion method, and the resulting cells were cultured in 1640 medium containing 20% calf serum and 1% penicillin/streptomycin. The isolated Kupffer cells were randomly divided into 4 groups: blank control group, TLR4 ligand activator LPS (1 μg/ml) group, LXRα ligand activator T0901317 (5 μg/ml) group, and LPS and T0901317 co-treatment group. The cultured cells were collected and Western bolting method was used to detect the LXRα, GRIP1 and IRF3 protein expression levels of Kupffer cells. ELISA was used to detect the contents of interferon (IFN)β, tumor necrosis factor (TNF)-α and interleukin (IL)-1β in Kupffer cell culture supernatant.
Results The expression level of LXRα protein was the highest in the T0901317 treatment group and the lowest in the LPS treatment group. In the combined treatment group, the expression of LXRα was significantly lower than that in the T0901317 treatment group (P<0.05), but also significantly higher than that of the T0901317 treatment group.�Two groups (P<0.05). The protein expression of IRF3 and GRIP1 was the highest in the LPS group, and the expression was significantly reduced in the combined treatment group. There were significant differences between the two groups (P<0.05); in the LPS group and the combined treatment group, the protein expression of IRF3 and GRIP1 was higher than that of the control group and T0901317 treatment group (P<0.05).
The IFNβ content in the LPS-treated group was significantly higher than that in the control group and T0901317-treated group (P<0.05); the IFNβ content in the combined treatment group was significantly lower than that in the LPS-treated group (P<0.05); IFNβ expression was the lowest in the T0901317-treated group. The content of TNF-α in the LPS-treated group was significantly higher than that in the other three groups (P0.05). The expression trend of IL-1β is the same as that of TNF-α. Conclusion The preventive application of LXRα agonist before LPS treatment can significantly inhibit the expression of IRF3 and GRIP1 in Kupffer cells, exert anti-inflammatory effects by inhibiting the expression of IRF3 and GRIP1, thereby inhibiting the activation of Kupffer cells induced by LPS.
References
[1] Hiscott J, Pitha P, Genin P, Nguyen H, Heylbroeck C, Mamane Y, Algarte M, Lin R (1999). “Triggering the interferon response: the role of IRF-3 transcription factor”.J .Interferon Cytokine Res.19(1):1–13.doi:10.1089/107999099314360.PMID 10048763.
[2] Lin R, Heylbroeck C, Genin P, Pitha PM, Hiscott J (Feb 1999). “Essential Role of Interferon Regulatory Factor 3 in Direct Activation of RANTES Chemokine Transcription”. Mol Cell Biol.19(2) :959–66.doi:10.1128/MCB.19.2.959.PMC 116027.PMID 9891032.
[3] Yoneyama M,Suhara W,Fujita T(2002).”Control of IRF-3 activation by phosphorylation”.J.Interferon Cytokine Res.22(1):73–6.doi:10.1089/107999002753452674. PMID 11846977.
[4] Collins SE, Noyce RS, Mossman KL (Feb 2004). “Innate Cellular Response to Virus Particle Entry Requires IRF3 but Not Virus Replication”.J Virol.78(4):1706–17.doi:10.1128 /JVI.78.4.1706-1717.2004.PMC 369475.PMID 14747536.
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[5 red phosphorus flame retardant] Hou F, Sun L, Zheng H, Skaug B, Jiang QX, Chen ZJ (Aug 5, 2011). “MAVS Forms Functional Prion-Like Aggregates To Activate and Propagate Antiviral Innate Immune Response”.Cell.146(3):448–61.doi:10.1016/j.cell.2011.06.041.PMC 3179916.PMID 21782231.
[6] LXRα negatively regulates the LPS-induced inflammatory response mechanism in Kupffer cells by downregulating IRF3 and GRIP1 [J]. Ou Zhibing, Huang Qingyong, Sun Ke, Wei Sidong, Gong Jianping, Tu Bing. Journal of Southern Medical University. 2009(05 )
