The coronavirus disease (COVID-19) has once again reminded us of the significance of host immune response and consequential havocs of the immune dysregulation. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) inflicts severe complications to the infected host, including cough, dyspnoea, fever, septic shock, acute respiratory distress syndrome (ARDs), and multiple organ failure. These manifestations are the consequence of the dysregulated immune system, which gives rise to excessive and unattended production of pro-inflammatory mediators. Elevated circulatory cytokine and chemokine levels are accompanied by spontaneous haemorrhage, thrombocytopenia and systemic inflammation, which are the cardinal features of life-threatening cytokine storm syndrome in advanced COVID-19 diseases. Coronavirus hijacked NF-kappa B (NF-κB) is responsible for upregulating the expressions of inflammatory cytokine, chemokine, alarmins and inducible enzymes, which paves the pathway for cytokine storm. Given the scenario, the systemic approach of simultaneous inhibition of NF-κB offers an attractive therapeutic intervention. Targeted therapies with proteasome inhibitor (VL-01, bortezomib, carfilzomib and ixazomib), bruton tyrosine kinase inhibitor (acalabrutinib), nucleotide analogue (remdesivir), TNF-α monoclonal antibodies (infliximab and adalimumab), N-acetylcysteine and corticosteroids (dexamethasone), focusing the NF-κB inhibition have demonstrated effectiveness in terms of the significant decrease in morbidity and mortality in severe COVID-19 patients. Hence, this review highlights the activation, signal transduction and cross-talk of NF-κB with regard to cytokine storm in COVID-19. Moreover, the development of therapeutic strategies based on NF-κB inhibition are also discussed herein.
【저자키워드】 COVID-19, SARS-CoV-2, Inflammation, Cytokine storm, COVID-19, Coronavirus disease 2019, Novel coronavirus, Severe acute respiratory syndrome, NF-κB, RSV, respiratory syncytial virus, JAK, Janus kinase, IL, interleukin, SARS, Severe acute respiratory syndrome, CoV, coronavirus, NK, natural killer, NO, Nitric Oxide, VEGF, Vascular endothelial growth factor, MAPK, Mitogen-activated protein kinase, ACE2, angiotensin-converting enzyme II, AT1R, activation of angiotensin-1-receptor, ADAM17, metalloprotease 17, BLC, B-lymphocyte chemoattractant, BAFFR, B-cell activating factor receptor, CD40+, cluster of differentiation 40, COX-2, cyclooxygenase-2, CXCL, C-X-C- motif chemokine, ALI, acute lung injuries, c-AMP, cyclic adenosine phosphate, CDC, Center for Disease Control and Prevention, CASP3, caspase 3, CXCL C-X-C, motif chemokine ligand, CRP C, reactive protein, CTLs, cytotoxic T lymphocytes, DAMP, damage-associated molecular patterns (DAMP), ERK1/2, extracellular signal-regulated kinases, TNF, Tumour Necrosis Factor, LPS, lipopolysaccharides, iNOS, nitric oxide synthase, NF-κB, nuclear factor kappa B cells, SMD, SOD, superoxide dismutase, TLR-4, Toll-like receptor-4, IP-10, interferon-inducible protein 10, MCP-1, monocyte chemoattractant protein 1, MIG, monokine induced by interferon-γ, MIP-1α and MIP-1β, macrophage inflammatory protein 1α and 1β, respectively, Th, helper T cells, PTMs, post-translational modifications, IL-1R, Interleukin 1 receptor (IL-1R), TNFR, tumour necrosis factor receptor, LTβR, Lymphotoxin-β receptor, RANK, receptor activator of NF-κB, IKK, IκB kinase, NEMO, regulatory subunit IKKγ, PKR, threonine-derived kinases, STAT3, signal transduction activator of transcription factor 3, STING, stimulator of interferon genes, MAPKs, mitogen-activated protein kinases, JNK, Jun amino-terminal kinases, CCL, chemokine ligand, PAMPs, pathogen-associated molecular patterns, GSDMD, Gasdermin, 【초록키워드】 Corticosteroid, Dexamethasone, coronavirus disease, therapy, Diseases, monoclonal antibody, Remdesivir, cytokine, Cytokine storm syndrome, immune system, cough, chemokine, Host immune response, Fever, Effectiveness, pathway, Septic shock, morbidity and mortality, systemic inflammation, multiple organ failure, inhibitor, Enzymes, expression, therapeutic strategy, Inflammatory cytokine, Signal transduction, TNF-α, NF-κB, Dyspnoea, acute respiratory distress, Coronavirus-2, nucleotide, manifestation, immune dysregulation, tyrosine, acute respiratory syndrome, Activation, syndrome, severe COVID-19 patients, life-threatening, therapeutic intervention, significant decrease, pro-inflammatory mediators, offer, Host, alarmin, approach, feature, highlight, responsible, demonstrated, dysregulated, upregulating, severe complication, accompanied, bortezomib, cross-talk, 【제목키워드】 NF-κB,