P021 Activation of interferon regulatory factor 5 in innate immune signaling by site specific phosphorylation

Cytokine ◽  
2012 ◽  
Vol 59 (3) ◽  
pp. 525
Author(s):  
H.C.C. Foreman ◽  
S. Van Scoy ◽  
T.-F. Cheng ◽  
N. Reich
2021 ◽  
Vol 12 ◽  
Author(s):  
Nicholas Stoy

Interleukin-1 receptor-associated kinase 4 (IRAK4) and interferon regulatory factor 5 (IRF5) lie sequentially on a signaling pathway activated by ligands of the IL-1 receptor and/or multiple TLRs located either on plasma or endosomal membranes. Activated IRF5, in conjunction with other synergistic transcription factors, notably NF-κB, is crucially required for the production of proinflammatory cytokines in the innate immune response to microbial infection. The IRAK4-IRF5 axis could therefore have a major role in the induction of the signature cytokines and chemokines of the hyperinflammatory state associated with severe morbidity and mortality in COVID-19. Here a case is made for considering IRAK4 or IRF5 inhibitors as potential therapies for the “cytokine storm” of COVID-19.


PLoS ONE ◽  
2012 ◽  
Vol 7 (3) ◽  
pp. e33098 ◽  
Author(s):  
Hui-Chen Chang Foreman ◽  
Sarah Van Scoy ◽  
Tsu-Fan Cheng ◽  
Nancy C. Reich

Author(s):  
Thirunavukkarasu Periyasamy ◽  
Ming-Wei Lu

Interferon regulatory factor 5 (IRF5) is known to be involved in the innate immune response and pro-inflammatory cytokines. However, the roles of IRF5 in immune responses in Malabar grouper (Epinephelus malabaricus) have not been extensively explored. In this study, IRF5 gene was identified and characterized from M. grouper. The full-length IRF5 cDNA consisted of a 5’ terminal untranslated region (5’-UTR) of 289 bp and a 3’-UTR of 542 bp, an open reading frame (ORF) of 1500 bp encoding a polypeptide of 499 amino acids with a predicted molecular mass of 56.28 kDa and isoelectric point (pI) of 5.2. The putative MgIRF5 protein consists of four important conserved domains: a helix DNA-binding domain (DBD) at the N-terminus, a middle region, an IRF association domain (IAD) and a virus activated domain (VAD) at the C-terminus. Sequence alignment and phylogenetic analysis showed that highest sequence similarity of IRF5 was observed between the IRF5 genes from Oplegnathus fasciatus and Miichthys miiuy. The mRNA transcripts of IRF5 were detected in a wide range of tissues types from healthy M. grouper with highest expression in muscle, liver and skin. After treatment with poly (I: C), it was significantly up-regulated in spleen and liver tissues. When infected with NNV, the expression level of MgIRF5 was up-regulated in spleen and head kidney and their transcriptional responses to IRF5 increased in the grouper kidney cells. This approach suggests that MgIRF5 is important in the underlying mechanism of the innate immune responses against antiviral response.


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