tetano
Editor, Senior Moderator
Am J Pathol. 2018 Jan 20. pii: S0002-9440(17)30866-0. doi: 10.1016/j.ajpath.2017.12.014. [Epub ahead of print]
[h=1]Galectin-3 enhances avian H5N1 influenza A virus-induced pulmonary inflammation by promoting NLRP3 inflammasome activation.[/h] Chen YJ[SUP]1[/SUP], Wang SF[SUP]2[/SUP], Weng IC[SUP]1[/SUP], Hong MH[SUP]1[/SUP], Lo TH[SUP]1[/SUP], Jan JT[SUP]3[/SUP], Hsu LC[SUP]4[/SUP], Chen HY[SUP]5[/SUP], Liu FT[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Highly pathogenic avian influenza A H5N1 virus causes pneumonia and acute respiratory distress syndrome in humans. Virus-induced excessive inflammatory response contributes to severe disease and high mortality rates. Galectin-3, a β-galactoside-binding protein widely distributed in immune and epithelial cells, regulates various immune functions and modulates microbial infections. Here we describe galectin-3 up-regulation in mouse lung tissue following challenges with the H5N1 influenza virus. We investigated the effects of endogenous galectin-3 on H5N1 infection and found that survival of galectin-3 knockout (Gal-3KO) mice was comparable to wild-type (WT) mice following infections. Compared to infected WT mice, infected Gal-3KO mice exhibited less inflammation in the lungs and reduced interleukin-1 beta (IL-1β) levels in bronchoalveolar lavage fluid. Also, the bone marrow-derived macrophages (BMMs) from Gal-3KO mice exhibited reduced oligomerization of apoptosis-associated speck-like proteins containing caspase-associated recruitment domains, and secreted less IL-1β compared to BMMs from WT mice. However, similar levels of the inflammasome component of nucleotide oligomerization domain-like receptor protein 3 (NLRP3) were observed in two genotypes of BMMs. Co-immunoprecipitation data indicated galectin-3 and NLRP3 interaction in BMMs infected with H5N1. An association was also observed between galectin-3 and NLRP3-ASC complex. Combined, our results suggest that endogenous galectin-3 enhances the effects of H5N1 infection by promoting host inflammatory responses and regulating IL-1β production by macrophages via interaction with NLRP3.
PMID: 29366678 DOI: 10.1016/j.ajpath.2017.12.014
[h=1]Galectin-3 enhances avian H5N1 influenza A virus-induced pulmonary inflammation by promoting NLRP3 inflammasome activation.[/h] Chen YJ[SUP]1[/SUP], Wang SF[SUP]2[/SUP], Weng IC[SUP]1[/SUP], Hong MH[SUP]1[/SUP], Lo TH[SUP]1[/SUP], Jan JT[SUP]3[/SUP], Hsu LC[SUP]4[/SUP], Chen HY[SUP]5[/SUP], Liu FT[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Highly pathogenic avian influenza A H5N1 virus causes pneumonia and acute respiratory distress syndrome in humans. Virus-induced excessive inflammatory response contributes to severe disease and high mortality rates. Galectin-3, a β-galactoside-binding protein widely distributed in immune and epithelial cells, regulates various immune functions and modulates microbial infections. Here we describe galectin-3 up-regulation in mouse lung tissue following challenges with the H5N1 influenza virus. We investigated the effects of endogenous galectin-3 on H5N1 infection and found that survival of galectin-3 knockout (Gal-3KO) mice was comparable to wild-type (WT) mice following infections. Compared to infected WT mice, infected Gal-3KO mice exhibited less inflammation in the lungs and reduced interleukin-1 beta (IL-1β) levels in bronchoalveolar lavage fluid. Also, the bone marrow-derived macrophages (BMMs) from Gal-3KO mice exhibited reduced oligomerization of apoptosis-associated speck-like proteins containing caspase-associated recruitment domains, and secreted less IL-1β compared to BMMs from WT mice. However, similar levels of the inflammasome component of nucleotide oligomerization domain-like receptor protein 3 (NLRP3) were observed in two genotypes of BMMs. Co-immunoprecipitation data indicated galectin-3 and NLRP3 interaction in BMMs infected with H5N1. An association was also observed between galectin-3 and NLRP3-ASC complex. Combined, our results suggest that endogenous galectin-3 enhances the effects of H5N1 infection by promoting host inflammatory responses and regulating IL-1β production by macrophages via interaction with NLRP3.
PMID: 29366678 DOI: 10.1016/j.ajpath.2017.12.014