Repurposing Methotrexate in Dampening SARS-CoV2-S1-Mediated IL6 Expression: Lessons Learnt from Lung Cancer

Autor: Pruthvi Gowda, Shanker Datt Joshi, Ellora Sen, Shruti Patrick, Rajesh Kumar Kumawat
Rok vydání: 2021
Předmět:
Lung Neoplasms
viruses
Anti-Inflammatory Agents
ACE2
Cytokine Receptor gp130
Immunology and Allergy
HMGB1 Protein
Phosphorylation
skin and connective tissue diseases
STAT3
medicine.diagnostic_test
biology
Folate-binding protein
respiratory system
medicine.anatomical_structure
Methotrexate
Spike Glycoprotein
Coronavirus
Adenocarcinoma
Original Article
Angiotensin-Converting Enzyme 2
medicine.symptom
Immunosuppressive Agents
medicine.drug
STAT3 Transcription Factor
Immunology
Adenocarcinoma of Lung
Inflammation
Western blot
Cell Line
Tumor
medicine
Humans
Folate Receptor 2
Lung cancer
Interleukin 6
IL-6
Lung
Interleukin-6
SARS-CoV-2
business.industry
COVID-19
Janus Kinase 1
Glycyrrhizic Acid
medicine.disease
COVID-19 Drug Treatment
respiratory tract diseases
A549 Cells
biology.protein
Cancer research
business
Zdroj: Inflammation
ISSN: 1573-2576
0360-3997
Popis: — Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) is associated with uncontrolled inflammatory responses. Loss of pulmonary angiotensin-converting enzyme 2 (ACE2) function has been associated with SARS-CoV-2 infection. The aberrant signalling and dysregulated inflammation characteristic of lung cancer have marked similarities with SARS-CoV-2 infection. Spearman’s correlation analysis of The Cancer Genome Atlas (TCGA) datasets indicated an inverse correlation between ACE2 and IL6 in lung adenocarcinoma. qRT-PCR analysis revealed CoV-2-SRBD-mediated diminished ACE2 expression in lung cancer cells that was concomitant with increased IL6 expression. Western blot and qRT-PCR analysis suggested that treatment with methotrexate (MTx) dampened CoV-2-SRBD-mediated increase in JAK1/STAT3 phosphorylation, gp130, IL6, and folate-binding protein (FBP) expressions. MTx also rescued the diminished expression of ACE2 in CoV-2-SRBD transfected cells. As lung tissue injury in severely affected COVID-19 patients is characterised by aberrant inflammatory response, repurposing MTx as an effective therapy against critical regulators of inflammation in SARS-CoV-2 infection warrants investigation.
Databáze: OpenAIRE
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