TBK1 and IKK[epsilon] are then free to phosphorylate IRF3
, which is activated upon phosphorylation and dimerisation and stimulates the production of type I interferons [48, 56].
On the other hand, the activity of IRF3
, a downstream nuclear transcription factor mediated by TRIF-dependent pathway, was also detected.
MAVS and TRIF signal via the kinases IKK and TBK1, resulting in translocation of the transcription factors NF-[kappa]B and IRF3
to the nucleus.
Lee, "Porcine reproductive and respiratory syndrome virus nucleocapsid protein modulates interferon production by inhibiting IRF3
activation in immortalized porcine alveolar macrophages," Archives of Virology, vol.
Antibodies against TLR4 (96kDa), MyD88 (33kDa), p65 (65kDa), pERK (4244kDa), TBK1 (80kDa), IRF3
(50kDa), protein C-reactive (PCR) (30kDa), and TNF[alpha] (27kDa) were purchased from Santa Cruz Biotechnology (Santa Cruz, CA); antibodies against CD14 (40 kDa), TRAF6 (55 kDa), TRIF (66 kDa), and IKKi/IKKe (80 kDa) were purchased from Abcam (Cambridge, UK); and antibodies against pIKK (85-87 kDa), pI[kappa]B (40 kDa), p38 (43 kDa), pP38 (43 kDa), and pIRF3 (45-55 kDa) were purchased from Cell Signaling Technology (Beverly, MA).
Jungi, "Type I IFN induction in response to Listeria monocytogenes in human macrophages: evidence for a differential activation of IFN regulatory factor 3 (IRF3
)," Journal of Immunology, vol.
Faia et al., "IKKE and TBKI are essential components of the IRF3
signalling pathway," Nature Immunology, vol.
On the other hand the interaction between RIP2 and TNF receptor associated factor 3 (TRAF3) induces type IIFN responses through nuclear translocation of interferon regulatory factor 3 (IRF3
) and IRF7.
After recognizing PAMPs by the TLR2 and 4 in a particular cell type, cytosolic TIR domain and associated adaptors (MyD88, TRIF, and SARM) are activated that in turn drive activation of the transcription factors such as NF-[kappa]B and/or IRF3
. Activation of these TLRs triggers two distinct signalling pathways viz.
Interferon regulatory factor 3 (IRF3
) and signal transducer and activator of transcription 3 (STAT3) have also been proposed to increase hepatic proinflammatory cytokines in ALD in association with oxidative stress, which needs further study to confirm.
Cell lysates (50 [micro]g protein) were resolved, transferred, and probed with TLR-4, TLR-2, myeloid differentiation factor 88 (MyD88), TRIF, and IRF3
antibodies as described previously .