Fig. 2.

Relationship between redox-sensitive TFs (NFκB, STAT3 and Nrf2). ROS/RNS are compounds, which are capable to maintain the long-time activity of redox-sensitive TFs even in the absence of action from other TFs inducers (receptor stimuli). ROS/RNS have been shown to activate canonical and non-canonical NFκB signalling pathways through alternative IκBα phosphorylation and through activating a critical redox-sensitive kinases (IKK, NIK). Nrf2 and STAT3 are also activated by oxidative/nitrosative stress and other stimuli. The Nrf2 repressor Keap1 can prevent NFκB activation by inhibiting the IKK. In addition to this, simultaneous activation of Nrf2 and NFκB results in the competition for CBP co-activators in the nucleus, in consequence of which these TFs suppress each other. In turn, STAT3 is capable to activate NFκB through stabilization of IKKα. Unphosphorylated STAT3 (following the activation of the STAT3 gene in response to ligands such as IL-6) can produce complex STAT3 with unphosphorylated p65/p50 heterodimer that activates promoters that have κB elements. The outcomes of ouoxidative/nitrosative stress may include NFκB and STAT3-dependent pro-inflammatory and pro-oxidant genes expression, as well as Nrf2-dependent anti-oxidant and cytoprotective genes expression. It is supposed that every pattern of inflammatory response (acute inflammation, LGSIP, HGSIP) with respect to the phase (response, resolution) can be characterized by different intensity of effects, which depend on the activity of redox-sensitive TFs. Note: Redox-sensitive proteins are shown in green; BAFFR – B-cell Activating Factor Receptor; BCR – B Cell Receptor: CREB – Cyclic AMP Response Element Binding Protein; CBP – CREB Binding Protein; IκB – NFκB Inhibitory Protein; IKK – IκB kinase; JAK – Janus Kinase; Keap1 – Kelch like ECH Associated Protein 1; LPS – Lipopolysaccharide; LTβR – Lymphotoxin β Receptor; NEMO – NFκB Essential Modulator (IKKγ); NFκB – Nuclear Factor κB; NIK – NFκB-Inducing Kinase; Nrf2 – Nuclear Factor Erythroid 2-Related Factor 2; P – Phosphorylation; RANK – Receptor Activator of NFκB; RANKL – Receptor Activator of NFκB Ligand; ROS – Reactive Oxygen Species; RNS – Reactive Nitrogen Species; STAT3 –Signal Transducer and Activator of Transcription 3; TAK1 – Transforming Growth factor-β-Activated Kinase; TCR – T Cell Receptor: TLRs – Toll-Like Receptors; TNFR –Tumour Necrosis Factor Receptor; Ub – Ubiquitination. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)