Surviving the storm: Dealing with COVID-19

Vandenbark, Arthur A.; Meza-Romero, Roberto; Offner, Halina

doi:10.1016/j.cellimm.2020.104153

Cited by 4 publications

(6 citation statements)

References 10 publications

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“…We identified several host proteins such as plastin-2, MIF, glutathione S-transferase A2, carbonic anhydrase 1 (CA1), and ADP-ribosylation factor 1 (ARF1) involved in the interleukin-12 signaling pathways. The MIF secreted in response to viral infection can activate the T cells and macrophages to produce inflammatory cytokines, including TNF-a, IL-6 and others, leading to elevated inflammatory response also called ''cytokine storm'' (Vandenbark, 2020). In our study, we have detected high levels of MIF, TNF-a and IL-6 in COVID-19 patients which correlates with the symptoms of acute respiratory distress syndrome (ARDS) in severe patients.…”

Section: Ll Open Access Isciencementioning

confidence: 57%

Proteomic investigation reveals dominant alterations of neutrophil degranulation and mRNA translation pathways in patients with COVID-19

Bankar¹,

Suvarna²,

Ghantasala³

et al. 2021

iScience

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The altered molecular proteins and pathways in response to COVID-19 infection are still unclear. Here, we performed a comprehensive proteomics-based investigation of nasopharyngeal swab samples from COVID-19 patients to study the host response by employing simple extraction strategies. Few of the host proteins such as Interleukin-6, L-lactate dehydrogenase, C-reactive protein, Ferritin and Aspartate aminotransferase were found to be up-regulated only in COVID-19 positive patients using targeted Multiple Reaction Monitoring studies. The most important pathways identified by enrichment analysis were neutrophil degranulation, interleukin-12 signaling pathways and mRNA translation of proteins thus providing the detailed investigation of host response in COVID-19 infection. Thus, we conclude that mass spectrometry-detected host proteins have a potential for disease severity progression; however, suitable validation strategies should be deployed for the clinical translation. Furthermore, the in-silico docking of host proteins involved in the interleukin-12 signaling pathway might aid in COVID-19 therapeutic interventions.

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Section: Ll Open Access Isciencementioning

confidence: 57%

Proteomic investigation reveals dominant alterations of neutrophil degranulation and mRNA translation pathways in patients with COVID-19

Bankar¹,

Suvarna²,

Ghantasala³

et al. 2021

iScience

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“…So far, the only known ligand of CD74 was the proinflammatory cytokine MIF, and MIF–CD74 interaction was shown to induce ZAP-70 signaling in B lymphoma cells ( 29 ). The clinical relevance of ligand-induced CD74 activity is demonstrated by clinical trials using anti-CD74 antibodies for the therapy of malignant B cell lymphoma ( 44 ) as well as studies aiming at interference with CD74–MIF signaling in the ongoing SARS-CoV-2 pandemic ( 22 ). Our finding that ZAP-70 signaling is also triggered upon interaction of TIMP-1 with CD74 suggests that TIMP-1 and MIF may exert similar cellular responses.…”

Section: Discussionmentioning

confidence: 99%

“…In an abstract for a symposium, without provision of experimental data ( 18 ), it was suggested that invariant chain (CD74) may be a possible interaction partner of TIMP-1. CD74 is, like TIMP-1, associated with inflammatory diseases ( 19 ) and is discussed as a therapeutic target in cancer ( 20 ) and autoimmune diseases ( 21 ) and notably also in the ongoing SARS-CoV-2 pandemic ( 22 ). CD74 plays an essential role in many biological processes ( 23 ), including antigen presentation ( 24 ) and B cell development ( 25 ).…”

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confidence: 99%

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Identification of invariant chain CD74 as a functional receptor of tissue inhibitor of metalloproteinases-1 (TIMP-1)

Schoeps

Eckfeld

Flüter

et al. 2021

Journal of Biological Chemistry

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Multifunctionality of tissue inhibitor of metalloproteinases-1 (TIMP-1) comprising antiproteolytic as well as cytokinic activity has been attributed to its N-terminal and C-terminal domains, respectively. The molecular basis of the emerging proinflammatory cytokinic activity of TIMP-1 is still not completely understood. The cytokine receptor invariant chain (CD74) is involved in many inflammation-associated diseases and is highly expressed by immune cells. CD74 triggers zeta chain–associated protein kinase-70 (ZAP-70) signaling–associated activation upon interaction with its only known ligand, the macrophage migration inhibitory factor. Here, we demonstrate TIMP-1–CD74 interaction by coimmunoprecipitation and confocal microscopy in cells engineered to overexpress CD74. In silico docking in HADDOCK predicted regions of the N-terminal domain of TIMP-1 (N-TIMP-1) to interact with CD74. This was experimentally confirmed by confocal microscopy demonstrating that recombinant N-TIMP-1 lacking the entire C-terminal domain was sufficient to bind CD74. Interaction of TIMP-1 with endogenously expressed CD74 was demonstrated in the Namalwa B lymphoma cell line by dot blot binding assays as well as confocal microscopy. Functionally, we demonstrated that TIMP-1–CD74 interaction triggered intracellular ZAP-70 activation. N-TIMP-1 was sufficient to induce ZAP-70 activation and interference with the cytokine-binding site of CD74 using a synthetic peptide–abrogated TIMP-1-mediated ZAP-70 activation. Altogether, we here identified CD74 as a receptor and mediator of cytokinic TIMP-1 activity and revealed TIMP-1 as moonlighting protein harboring both cytokinic and antiproteolytic activity within its N-terminal domain. Recognition of this functional TIMP-1–CD74 interaction may shed new light on clinical attempts to therapeutically target ligand-induced CD74 activity in cancer and other inflammatory diseases.

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“…This causes chronic inflammation and neuronal damage. The development of new-generation immunologically based cytokine storm inhibitors is a promising tool for controlling inflammation during COVID-19 infection [10].…”

Section: Mechanisms Of Sars-cov-2 Neuroinvasion and Neurological Damagementioning

confidence: 99%

SARS-CoV-2 Infection: Symptoms of the Nervous System and Implications for Therapy in Neurological Disorders

Losy

2020

Neurol Ther

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In this paper, the neurological aspects of COVID-19 are presented, which may be of significance for physicians. Knowledge about the neurological symptoms of COVID-19 infection should help physicians in diagnoses and in taking appropriate precautions, as some manifestations can appear before typical pulmonary symptoms. Various mechanisms of SARS-CoV-2 neuroinvasion are discussed and symptoms are described, which can be subdivided into manifestations of the central nervous system (CNS) (headache, dizziness, stroke, impaired consciousness, encephalitis, meningitis, seizures) and peripheral nervous system (PNS) (characteristic hyposmia and hypogeusia, Guillain Barré syndrome, myalgia). Additionally, the implications of COVID-19 infection for treatment of patients with common neurological diseases and their management is presented. It can be concluded that neurological symptoms are part of a clinical spectrum of COVID-19 infection, involving the CNS and PNS. COVID-19 may influence decisions regarding the treatment of neurological disorders, especially those with an immune background.

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Surviving the storm: Dealing with COVID-19

Cited by 4 publications

References 10 publications

Proteomic investigation reveals dominant alterations of neutrophil degranulation and mRNA translation pathways in patients with COVID-19

Proteomic investigation reveals dominant alterations of neutrophil degranulation and mRNA translation pathways in patients with COVID-19

Identification of invariant chain CD74 as a functional receptor of tissue inhibitor of metalloproteinases-1 (TIMP-1)

SARS-CoV-2 Infection: Symptoms of the Nervous System and Implications for Therapy in Neurological Disorders

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