Repurposing Methotrexate in Dampening SARS-CoV2-S1-Mediated IL6 Expression: Lessons Learnt from Lung Cancer
العنوان: | Repurposing Methotrexate in Dampening SARS-CoV2-S1-Mediated IL6 Expression: Lessons Learnt from Lung Cancer |
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المؤلفون: | Pruthvi Gowda, Shanker Datt Joshi, Ellora Sen, Shruti Patrick, Rajesh Kumar Kumawat |
المصدر: | Inflammation |
بيانات النشر: | Springer Science and Business Media LLC, 2021. |
سنة النشر: | 2021 |
مصطلحات موضوعية: | 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 |
الوصف: | — 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. |
تدمد: | 1573-2576 0360-3997 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dd99e986fdfefd052b3cef0bd12b1539 https://doi.org/10.1007/s10753-021-01536-6 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....dd99e986fdfefd052b3cef0bd12b1539 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15732576 03603997 |
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