Author: Michael Jay Corley; Christopher Sugai; Michael Schotsaert; Robert E. Schwartz; Lishomwa C Ndhlovu
Title: Comparative in vitro transcriptomic analyses of COVID-19 candidate therapy hydroxychloroquine suggest limited immunomodulatory evidence of SARS-CoV-2 host response genes. Document date: 2020_4_14
ID: 30x26ip7_11
Snippet: Low Density Lipoprotein Receptor (LDLR) genes, which were transcriptionally altered in the HCQ treatment of PBMC transcriptional dataset (Fig.1c ,f) and in the SARS-CoV-2 in vitro infection of NHBE cells transcriptional dataset (Fig.1d,g) . Interestingly, the NDRG2 and LDLR genes were not altered upon SARS-CoV-2 in vitro infection of A549 cells (Fig.1e,h) , suggesting different in vitro SARS-CoV-2 infection models vary in transcriptional response.....
Document: Low Density Lipoprotein Receptor (LDLR) genes, which were transcriptionally altered in the HCQ treatment of PBMC transcriptional dataset (Fig.1c ,f) and in the SARS-CoV-2 in vitro infection of NHBE cells transcriptional dataset (Fig.1d,g) . Interestingly, the NDRG2 and LDLR genes were not altered upon SARS-CoV-2 in vitro infection of A549 cells (Fig.1e,h) , suggesting different in vitro SARS-CoV-2 infection models vary in transcriptional responses which will be critical for identifying relevant host genes impacted by viral infection. The NDRG2 gene has been identified as a novel factor for the regulation of IL-10 in myeloid cells [16] and a factor in macrophage polarization [17] , suggesting HCQ may impact myeloid cell inflammation that has been hypothesized as a driver of severe COVID-19 [18] . We observed that NDRG2 was significantly upregulated in the SARS-CoV-2 in vitro infection dataset (Fig.1d ) and significantly downregulated in the in vitro hydroxychloroquine treatment dataset (Fig.1c) , suggesting that HCQ may restore host transcription of NDRG2 and exert anti-inflammatory effects. We found that the LDLR gene was significantly upregulated in both the in vitro hydroxychloroquine treatment and SARS-CoV-2 infection datasets ( Fig.1f ,g), suggesting both HCQ treatment and SARS-CoV-2 infection alter lipid metabolism transcription. We acknowledge these observations are associative and further casual studies are needed. Previous work has shown HCQ impacts lipid profiles [19] by potentially altering intracellular pH leading to lipid uptake and increased receptor expression.
Search related documents:
Co phrase search for related documents- anti inflammatory effect and HCQ impact: 1
- anti inflammatory effect and HCQ treatment: 1
- anti inflammatory effect and increased receptor expression: 1
- anti inflammatory effect and lipid profile: 1
- anti inflammatory effect and macrophage polarization: 1
- anti inflammatory effect and receptor expression: 1, 2, 3, 4
- anti inflammatory effect and SARS infection: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19
- anti inflammatory effect and SARS infection model: 1
- anti inflammatory effect and viral infection: 1, 2, 3, 4, 5, 6, 7, 8
- anti inflammatory effect and vitro infection: 1
- anti inflammatory effect exert and cell inflammation: 1
- anti inflammatory effect exert and macrophage polarization: 1
Co phrase search for related documents, hyperlinks ordered by date