scholarly journals Remdesivir and Cyclosporine Synergistically Inhibit the Human Coronaviruses OC43 and SARS-CoV-2

2021 ◽  
Vol 12 ◽  
Author(s):  
Hsing-Yu Hsu ◽  
Cheng-Wei Yang ◽  
Yue-Zhi Lee ◽  
Yi-Ling Lin ◽  
Sui-Yuan Chang ◽  
...  
Keyword(s):  
Calcineurin Inhibitor ◽  
Human Lung ◽  
Immunofluorescence Assay ◽  
Plaque Formation ◽  
Lung Fibroblasts ◽  
Cytokine Storm ◽  
Rna Dependent Rna Polymerase ◽  
Human Coronavirus ◽  
Human Lung Fibroblasts ◽  
Human Coronaviruses

Remdesivir, a prodrug targeting RNA-dependent-RNA-polymerase, and cyclosporine, a calcineurin inhibitor, individually exerted inhibitory activity against human coronavirus OC43 (HCoV-OC43) in HCT-8 and MRC-5 cells at EC50 values of 96 ± 34 ∼ 85 ± 23 nM and 2,920 ± 364 ∼ 4,419 ± 490 nM, respectively. When combined, these two drugs synergistically inhibited HCoV-OC43 in both HCT-8 and MRC-5 cells assayed by immunofluorescence assay (IFA). Remdesivir and cyclosporine also separately reduced IL-6 production induced by HCoV-OC43 in human lung fibroblasts MRC-5 cells with EC50 values of 224 ± 53 nM and 1,292 ± 352 nM, respectively; and synergistically reduced it when combined. Similar trends were observed for SARS-CoV-2, which were 1) separately inhibited by remdesivir and cyclosporine with respective EC50 values of 3,962 ± 303 nM and 7,213 ± 143 nM by IFA, and 291 ± 91 nM and 6,767 ± 1,827 nM by a plaque-formation assay; and 2) synergistically inhibited by their combination, again by IFA and plaque-formation assay. Collectively, these results suggest that the combination of remdesivir and cyclosporine merits further study as a possible treatment for COVID-19 complexed with a cytokine storm.

scholarly journals Fenofibrate inhibits TGF‐β‐induced myofibroblast differentiation and activation in human lung fibroblasts in vitro

FEBS Open Bio ◽  
2021 ◽  
Author(s):  
Ryota Kikuchi ◽  
Yuki Maeda ◽  
Takao Tsuji ◽  
Kazuhiro Yamaguchi ◽  
Shinji Abe ◽  
...  
Keyword(s):  
Human Lung ◽  
Lung Fibroblasts ◽  
Myofibroblast Differentiation ◽  
Human Lung Fibroblasts

scholarly journals Procollagen production and procollagen messenger RNA levels and activity in human lung fibroblasts during periods of rapid and stationary growth.

1981 ◽  
Vol 256 (6) ◽  
pp. 3135-3140
Author(s):  
P. Tolstoshev ◽  
R.A. Berg ◽  
S.I. Rennard ◽  
K.H. Bradley ◽  
B.C. Trapnell ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Human Lung ◽  
Lung Fibroblasts ◽  
Stationary Growth ◽  
Human Lung Fibroblasts ◽  
Rna Levels

scholarly journals Identification of TGF-β receptor-1 as a key regulator of carbon nanotube-induced fibrogenesis

2015 ◽  
Vol 309 (8) ◽  
pp. L821-L833 ◽  
Author(s):  
Anurag Mishra ◽  
Todd A. Stueckle ◽  
Robert R. Mercer ◽  
Raymond Derk ◽  
Yon Rojanasakul ◽  
...  
Keyword(s):  
Lung Fibrosis ◽  
Human Lung ◽  
Lung Fibroblasts ◽  
Screening Tests ◽  
Rapid Screening ◽  
Interstitial Tissue ◽  
Collagen Production ◽  
Human Lung Fibroblasts ◽  
Β Receptor ◽  
Tgf Β1

Carbon nanotubes (CNTs) induce rapid interstitial lung fibrosis, but the underlying mechanisms are unclear. Previous studies indicated that the ability of CNTs to penetrate lung epithelium, enter interstitial tissue, and stimulate fibroblasts to produce collagen matrix is important to lung fibrosis. In this study, we investigated the activation of transforming growth factor-β receptor-1 [TGF-β R1; i.e., activin receptor-like kinase 5 (ALK5) receptor] and TGF-β/Smad signaling pathway in CNT-induced collagen production in human lung fibroblasts. Human lung fibroblasts and epithelial cells were exposed to low, physiologically relevant concentrations (0.02–0.6 μg/cm2) of single-walled CNTs (SWCNT) and multiwalled CNTs (MWCNT) in culture and analyzed for collagen, TGF-β1, TGF-β R1, and SMAD proteins by Western blotting and immunofluorescence. Chemical inhibition of ALK5 and short-hairpin (sh) RNA targeting of TGF-β R1 and Smad2 were used to probe the fibrogenic mechanism of CNTs. Both SWCNT and MWCNT induced an overexpression of TGF-β1, TGF-β R1 and Smad2/3 proteins in lung fibroblasts compared with vehicle or ultrafine carbon black-exposed controls. SWCNT- and MWCNT-induced collagen production was blocked by ALK5 inhibitor or shRNA knockdown of TGF-β R1 and Smad2. Our results indicate the critical role of TGF-β R1/Smad2/3 signaling in CNT-induced fibrogenesis by upregulating collagen production in lung fibroblasts. This novel finding may aid in the design of mechanism-based risk assessment and development of rapid screening tests for nanomaterial fibrogenicity.

scholarly journals MORPHOGENETIC ASPECTS OF MULTILAYERING IN PETRI DISH CULTURES OF HUMAN FETAL LUNG FIBROBLASTS

1969 ◽  
Vol 41 (1) ◽  
pp. 298-311 ◽  
Author(s):  
Tom Elsdale ◽  
Robert Foley
Keyword(s):  
Extracellular Matrix ◽  
Human Lung ◽  
Petri Dish ◽  
Fetal Lung ◽  
Single Species ◽  
Lung Fibroblasts ◽  
Human Lung Fibroblasts ◽  
Spontaneous Aggregation ◽  
Control Hypothesis ◽  
Human Fetal Lung

Randomly seeded Petri dish cultures of embryonic human lung fibroblasts generate, in the course of their growth, highly ordered cellular arrangements. Thick, bilaterally symmetrical ridges with an axial polarity and an orthogonal, multilayered internal organization are observed within stationary cultures. The generation of these structures has been investigated. Ridges result from the spontaneous aggregation of cells in postconfluent cultures brought about by directed cell movements. These movements are promoted by the localized production of extracellular matrix sheets containing collagen, which provide new substrates for cellular colonization. Cells that have colonized one matrix substrate may secrete another above themselves, which will in turn be colonized. By a continuation of this cycle, thick stacks consisting of alternate layers of cells and matrix are produced to yield the observed aggregations. The distribution and shape of ridges in a culture imply that matrix substrates are confined to specific locations. The suggested control hypothesis assumes that all the cells in fibroblast cultures are potential producers of a single species of matrix. The serviceability of this matrix as a substrate for cellular colonization, however, is destroyed if the producer cells are motile. Matrix substrates, therefore, are only made by nonmotile cells.

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