In vitro induction of interleukin-8 by SARS-CoV-2 Spike protein is inhibited in bronchial epithelial IB3-1 cells by a miR-93-5p agomiR

In this study, we investigated the role of dimethyl sulfoxide (DMSO) in inhibiting interleukin-8 (IL-8)-mediated neutrophil recruitment induced by Pseudomonas aeruginosa (PA) bacterial supernatant. First, we tested whether DMSO could inhibit IL-8 production induced by PA in human bronchial epithelial (16-HBE) cells in vitro. In these cells, exposure to PA or H2O2 induced IL-8 production dose dependently, an effect that was inhibited by 1% DMSO at both the protein and RNA level. Second, we tested whether DMSO could block the recruitment of neutrophils induced by PA in a bypassed segment of dog trachea in vivo. PA supernatant was placed in the tracheal segment for 6 h in four dogs, and neutrophil recruitment and IL-8 concentrations were measured in the superfusate. DMSO prevented the recruitment of neutrophils and IL-8 production induced by PA time dependently. The results suggest that DMSO may play an anti-inflammatory role in the airway by inhibiting IL-8 production in epithelial cells.

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Sulforaphane inhibits the expression of interleukin-6 and interleukin-8 induced in bronchial epithelial IB3-1 cells by exposure to the SARS-CoV-2 Spike protein

Phytomedicine ◽

10.1016/j.phymed.2021.153583 ◽

2021 ◽

pp. 153583

Author(s):

Jessica Gasparello ◽

Elisabetta D'Aversa ◽

Chiara Papi ◽

Laura Gambari ◽

Brunella Grigolo ◽

...

Keyword(s):

Interleukin 6 ◽

Interleukin 8 ◽

Spike Protein ◽

Bronchial Epithelial

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Discovery and in-vitro evaluation of potent SARS-CoV-2 entry inhibitors

10.1101/2021.04.02.438204 ◽

2021 ◽

Author(s):

Arpan Acharya ◽

Kabita Pandey ◽

Michellie Thurman ◽

Elizabeth Klug ◽

Jay Trivedi ◽

...

Keyword(s):

Virus Entry ◽

Vero Cells ◽

Spike Protein ◽

Entry Inhibitor ◽

Receptor Binding Domain ◽

Human Bronchial Epithelial Cells ◽

Computer Aided Drug Design ◽

Bronchial Epithelial ◽

Entry Inhibitors

SARS-CoV-2 infection initiates with the attachment of spike protein to the ACE2 receptor. While vaccines have been developed, no SARS-CoV-2 specific small molecule inhibitors have been approved. Herein, utilizing the crystal structure of the ACE2/Spike receptor binding domain (S-RBD) complex in computer-aided drug design (CADD) approach, we docked ~8 million compounds within the pockets residing at S-RBD/ACE2 interface. Five best hits depending on the docking score, were selected and tested for their in vitro efficacy to block SARS-CoV-2 replication. Of these, two compounds (MU-UNMC-1 and MU-UNMC-2) blocked SARS-CoV-2 replication at sub-micromolar IC50 in human bronchial epithelial cells (UNCN1T) and Vero cells. Furthermore, MU-UNMC-2 was highly potent in blocking the virus entry by using pseudoviral particles expressing SARS-CoV-2 spike. Finally, we found that MU-UNMC-2 is highly synergistic with remdesivir (RDV), suggesting that minimal amounts are needed when used in combination with RDV, and has the potential to develop as a potential entry inhibitor for COVID-19.

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Nitrite Reductase from Pseudomonas aeruginosa Released by Antimicrobial Agents and Complement Induces Interleukin-8 Production in Bronchial Epithelial Cells

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.43.4.794 ◽

1999 ◽

Vol 43 (4) ◽

pp. 794-801 ◽

Cited By ~ 3

Author(s):

Borann Sar ◽

Kazunori Oishi ◽

Akihiro Wada ◽

Toshiya Hirayama ◽

Kouji Matsushima ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Epithelial Cells ◽

Nitrite Reductase ◽

Antimicrobial Agents ◽

Bacterial Culture ◽

Neutrophil Migration ◽

Bronchial Epithelial Cells ◽

Interleukin 8 ◽

Bronchial Epithelial

ABSTRACT We have recently reported that nitrite reductase, a bifunctional enzyme located in the periplasmic space of Pseudomonas aeruginosa, could induce interleukin-8 (IL-8) generation in a variety of respiratory cells, including bronchial epithelial cells (K. Oishi et al. Infect. Immun. 65:2648–2655, 1997). In this report, we examined the mode of nitrite reductase (PNR) release from a serum-sensitive strain of live P. aeruginosa cells during in vitro treatment with four different antimicrobial agents or human complement. Bacterial killing ofP. aeruginosa by antimicrobial agents induced PNR release and mediated IL-8 production in human bronchial epithelial (BET-1A) cells. Among these agents, imipenem demonstrated rapid killing of P. aeruginosa as well as rapid release of PNR and resulted in the highest IL-8 production. Complement-mediated killing of P. aeruginosa was also associated with PNR release and enhanced IL-8 production. The immunoprecipitates of the aliquots of bacterial culture containing imipenem or complement with anti-PNR immunoglobulin G (IgG) induced a twofold-higher IL-8 production than did the immunoprecipitates of the aliquots of bacterial culture with a control IgG. These pieces of evidence confirmed that PNR released in the aliquots of bacterial culture was responsible for IL-8 production in the BET-1A cells. Furthermore, the culture supernatants of the BET-1A cells stimulated with aliquots of bacterial culture containing antimicrobial agents or complement similarly mediated neutrophil migration in vitro. These data support the possibility that a potent inducer of IL-8, PNR, could be released fromP. aeruginosa after exposure to antimicrobial agents or complement and contributes to neutrophil migration in the airways during bronchopulmonary infections with P. aeruginosa.

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RU 41740 (BiostimR) stimulates the production of granulocyte macrophage colony-stimulating factor and interleukin-8 by human bronchial epithelial cells in vitro

General Pharmacology The Vascular System ◽

10.1016/s0306-3623(96)00086-9 ◽

1996 ◽

Vol 27 (8) ◽

pp. 1351-1353

Author(s):

R. Aloui ◽

F. Gormand ◽

B. Guibert ◽

F. Corallo ◽

M. Perrin Fayolle ◽

...

Keyword(s):

Epithelial Cells ◽

Bronchial Epithelial Cells ◽

Interleukin 8 ◽

Colony Stimulating Factor ◽

Human Bronchial Epithelial Cells ◽

Bronchial Epithelial ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor

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Antihistamines and production of granulocyte-macrophage colony-stimulating factor and interleukin-8 by human bronchial epithelial cells in vitro: Evaluation of the effects of loratadine and cetirizine

General Pharmacology The Vascular System ◽

10.1016/0306-3623(95)02009-8 ◽

1996 ◽

Vol 27 (2) ◽

pp. 269-272 ◽

Cited By ~ 4

Author(s):

C. Amsellem ◽

F. Gormand ◽

R. Hosni ◽

R. Aloui ◽

B. Guibert ◽

...

Keyword(s):

Epithelial Cells ◽

Bronchial Epithelial Cells ◽

Interleukin 8 ◽

Colony Stimulating Factor ◽

Human Bronchial Epithelial Cells ◽

Bronchial Epithelial ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor

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In Vitro Induction of Crystals of MT Protein by Vinblastine-Colcemid in Mouse Spermatids

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100050676 ◽

1974 ◽

Vol 32 ◽

pp. 132-133

Author(s):

John J. Wolosewick ◽

John H. D. Bryan

Keyword(s):

Endoplasmic Reticulum ◽

Smooth Endoplasmic Reticulum ◽

Nuclear Ring ◽

Rough Er ◽

Distal Direction ◽

In Vitro Induction

Early in spermiogenesis the manchette is rapidly assembled in a distal direction from the nuclear-ring-densities. The association of vesicles of smooth endoplasmic reticulum (SER) and the manchette microtubules (MTS) has been reported. In the mouse, osmophilic densities at the distal ends of the manchette are the organizing centers (MTOCS), and are associated with the SER. Rapid MT assembly and the lack of rough ER suggests that there is an existing pool of MT protein. Colcemid potentiates the reaction of vinblastine with tubulin and was used in this investigation to detect this protein.

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