tetano
Editor, Senior Moderator
Mucosal Immunol. 2016 Dec 14. doi: 10.1038/mi.2016.107. [Epub ahead of print]
[h=1]IL-36 receptor deletion attenuates lung injury and decreases mortality in murine influenza pneumonia.[/h] Aoyagi T[SUP]1,[/SUP][SUP]2[/SUP], Newstead MW[SUP]1[/SUP], Zeng X[SUP]1[/SUP], Kunkel SL[SUP]3[/SUP], Kaku M[SUP]2[/SUP], Standiford TJ[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza virus causes a respiratory disease in humans that can progress to lung injury with fatal outcome. The interleukin (IL)-36 cytokines are newly described IL-1 family cytokines that promote inflammatory responses via binding to the IL-36 receptor (IL-36R). The mechanism of expression and the role of IL-36 cytokines are poorly understood. Here, we investigated the role of IL-36 cytokines in modulating the innate inflammatory response during influenza virus-induced pneumonia in mice. The intranasal administration of influenza virus upregulated IL-36α mRNA and protein production in the lungs. In vitro, influenza virus-mediated IL-36α but not IL-36γ is induced and secreted from alveolar epithelial cells (AECs) through both a caspase-1 and caspase-3/7 dependent pathway. IL-36α was detected in microparticles shed from AECs and promoted the production of pro-inflammatory cytokines and chemokines in respiratory cells. IL-36R-deficient mice were protected from influenza virus-induced lung injury and mortality. Decreased mortality was associated with significantly reduced early accumulation of neutrophils and monocytes/macrophages, activation of lymphocytes, production of pro-inflammatory cytokines and chemokines, and permeability of the alveolar-epithelial barrier in despite impaired viral clearance. Taken together, these data indicate that IL-36 ligands exacerbate lung injury during influenza virus infection.Mucosal Immunology advance online publication 14 December 2016; doi:10.1038/mi.2016.107.
PMID: 27966554 DOI: 10.1038/mi.2016.107
[PubMed - as supplied by publisher]
[h=1]IL-36 receptor deletion attenuates lung injury and decreases mortality in murine influenza pneumonia.[/h] Aoyagi T[SUP]1,[/SUP][SUP]2[/SUP], Newstead MW[SUP]1[/SUP], Zeng X[SUP]1[/SUP], Kunkel SL[SUP]3[/SUP], Kaku M[SUP]2[/SUP], Standiford TJ[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza virus causes a respiratory disease in humans that can progress to lung injury with fatal outcome. The interleukin (IL)-36 cytokines are newly described IL-1 family cytokines that promote inflammatory responses via binding to the IL-36 receptor (IL-36R). The mechanism of expression and the role of IL-36 cytokines are poorly understood. Here, we investigated the role of IL-36 cytokines in modulating the innate inflammatory response during influenza virus-induced pneumonia in mice. The intranasal administration of influenza virus upregulated IL-36α mRNA and protein production in the lungs. In vitro, influenza virus-mediated IL-36α but not IL-36γ is induced and secreted from alveolar epithelial cells (AECs) through both a caspase-1 and caspase-3/7 dependent pathway. IL-36α was detected in microparticles shed from AECs and promoted the production of pro-inflammatory cytokines and chemokines in respiratory cells. IL-36R-deficient mice were protected from influenza virus-induced lung injury and mortality. Decreased mortality was associated with significantly reduced early accumulation of neutrophils and monocytes/macrophages, activation of lymphocytes, production of pro-inflammatory cytokines and chemokines, and permeability of the alveolar-epithelial barrier in despite impaired viral clearance. Taken together, these data indicate that IL-36 ligands exacerbate lung injury during influenza virus infection.Mucosal Immunology advance online publication 14 December 2016; doi:10.1038/mi.2016.107.
PMID: 27966554 DOI: 10.1038/mi.2016.107
[PubMed - as supplied by publisher]