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

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Inflammation


. 2021 Sep 3.
doi: 10.1007/s10753-021-01536-6. Online ahead of print.
Repurposing Methotrexate in Dampening SARS-CoV2-S1-Mediated IL6 Expression: Lessons Learnt from Lung Cancer


Pruthvi Gowda ¹ , Shruti Patrick ¹ , Shanker Datt Joshi ¹ , Rajesh Kumar Kumawat ¹ , Ellora Sen ^{2 2}



Affiliations

• PMID: 34480250
• DOI: 10.1007/s10753-021-01536-6

Abstract

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.

Keywords: ACE2; COVID-19; Folate-binding protein; IL-6; Methotrexate..