tetano
Editor, Senior Moderator
PLoS One. 2018 Oct 10;13(10):e0205344. doi: 10.1371/journal.pone.0205344. eCollection 2018.
[h=1]Inhibition of autophagy and chemokine induction by sphingosine 1-phosphate receptor 1 through NF-κB signaling in human pulmonary endothelial cells infected with influenza A viruses.[/h] Wang L[SUP]1,[/SUP][SUP]2[/SUP], Jiang H[SUP]3[/SUP], Shen SM[SUP]1[/SUP], Wen CX[SUP]4[/SUP], Xing Z[SUP]5,[/SUP][SUP]4[/SUP], Shi Y[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Endothelial cells have been considered the central regulators of cytokine storm in the respiratory system during influenza virus infection. Studies have found that elevated autophagy could be an essential component of viral pathogenesis in influenza infection. However, few studies have been performed to examine whether autophagy occurs in human pulmonary endothelial cells (HPMECs). In addition, specific mechanisms about how inflammatory responses are regulated in the endothelial cells remain unclear. We hypothesized that infection of influenza A viruses subtypes H1N1 and H9N2 triggered autophagy, which played an important role in the induction of proinflammatory cytokines, both in human lung epithelial A549 cells and in HPMECs. In this report, we showed our evidence that blockage of autophagy significantly inhibited influenza virus-induced proinflammatory responses and suppressed viral replication. Our data indicated that the inhibition of the cytokine response and viral replication was affected by increasing the expression of endothelial sphingosine 1-phosphate receptor 1 (S1PR1), which might be through the regulation of NF-κB signaling. Overexpression of S1PR1 decreased p65 phosphorylation and translocation into the nucleus. Furthermore, we demonstrated that S1PR1 stimulation inhibited Akt-mTOR signaling, which might contribute to activation of autophagy in HPMECs. Thus, our study provides knowledge crucial to better understanding novel mechanisms underlying the S1PR1-mediated attenuation of cytokine amplification in the pulmonary system during influenza virus infection.
PMID: 30304001 DOI: 10.1371/journal.pone.0205344
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[h=1]Inhibition of autophagy and chemokine induction by sphingosine 1-phosphate receptor 1 through NF-κB signaling in human pulmonary endothelial cells infected with influenza A viruses.[/h] Wang L[SUP]1,[/SUP][SUP]2[/SUP], Jiang H[SUP]3[/SUP], Shen SM[SUP]1[/SUP], Wen CX[SUP]4[/SUP], Xing Z[SUP]5,[/SUP][SUP]4[/SUP], Shi Y[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Endothelial cells have been considered the central regulators of cytokine storm in the respiratory system during influenza virus infection. Studies have found that elevated autophagy could be an essential component of viral pathogenesis in influenza infection. However, few studies have been performed to examine whether autophagy occurs in human pulmonary endothelial cells (HPMECs). In addition, specific mechanisms about how inflammatory responses are regulated in the endothelial cells remain unclear. We hypothesized that infection of influenza A viruses subtypes H1N1 and H9N2 triggered autophagy, which played an important role in the induction of proinflammatory cytokines, both in human lung epithelial A549 cells and in HPMECs. In this report, we showed our evidence that blockage of autophagy significantly inhibited influenza virus-induced proinflammatory responses and suppressed viral replication. Our data indicated that the inhibition of the cytokine response and viral replication was affected by increasing the expression of endothelial sphingosine 1-phosphate receptor 1 (S1PR1), which might be through the regulation of NF-κB signaling. Overexpression of S1PR1 decreased p65 phosphorylation and translocation into the nucleus. Furthermore, we demonstrated that S1PR1 stimulation inhibited Akt-mTOR signaling, which might contribute to activation of autophagy in HPMECs. Thus, our study provides knowledge crucial to better understanding novel mechanisms underlying the S1PR1-mediated attenuation of cytokine amplification in the pulmonary system during influenza virus infection.
PMID: 30304001 DOI: 10.1371/journal.pone.0205344
Free full text