S1PR1 regulates NDV-induced IL-1β expression via NLRP3/caspase-1 inflammasome

Abstract

Newcastle disease (ND) is an acute, febrile, and highly contagious disease caused by the Newcastle disease virus (NDV), an important pathogen harmful to domestic poultry. Virulent NDV strain infection induces IL-1β expression and along with strong inflammatory response, ultimately results in death. Inhibition or overexpression of S1PR1, an important target for inflammatory disease treatment, regulates IL-1β expression, suggesting that S1PR1 may alter the degree of the inflammatory response induced by NDV infection by regulating pro-inflammatory cytokine expression. However, the molecular mechanism by which S1PR1 regulates IL-1β expression remains unclear. Here, we explore the expression and tissue distribution of S1PR1 after NDV infection and found that S1PR1 expression increased in the lungs, bursa of Fabricius, and DF-1. IL-1β expression induced by NDV was increased following treatment of cells with the S1PR1-specific agonist, SEW2871. In contrast, IL-1β expression induced by NDV was decreased after cells were treated with the S1PR1 inhibitor W146, suggesting that S1PR1 promotes NDV-induced IL-1β expression. Further investigation demonstrated that NDV induced IL-1β expression through p38, JNK/MAPK, and NLRP3/caspase-1 signaling molecules and S1PR1 affected the expression of IL-1β by activating the NLRP3/caspase-1 inflammasome but had no significant effect on p38 and JNK/MAPK. Our study shows that NDV infection promotes S1PR1 expression and induces IL-1β expression through p38, JNK/MAPK, and NLRP3/caspase-1 inflammasomes and that S1PR1 regulates IL-1β expression mainly through the NLRP3/caspase-1 inflammasome.

NDV-induced autophagy enhances inflammation through NLRP3/Caspase-1 inflammasomes and the p38/MAPK pathway

“…NDV induces a severe inflammatory response, further aggravating the cytopathic effects of NDV infection [ 22 , 23 ]. Several studies have shown a close relationship between autophagy and inflammation [ 8 , 24 , 25 , 29 ].…”

“…Several studies have shown that in addition to the NLRP3 inflammasome, various signaling pathways regulate inflammatory cytokines, including ERK1/2, JNK, and p38/MAPK [ 23 , 38 , 39 ]. We assessed the expression of essential proteins in these pathways to explore other mechanisms involved in regulating the inflammatory response by NDV-induced autophagy.…”

“…Cells were digested with trypsin, centrifuged with cell culture supernatants at 1000 rpm for 5 min at 4 °C, and washed once with PBS. Then, the cell pellet was collected, lysed, and centrifuged at 20 000 rpm for 20 min at 4 °C, and the activity of Caspase-1 was determined based on the ability of Caspase-1 to convert acetyl-Tyr-Val-Ala-Asp p-nitroaniline (Ac-YVAD-pNA) into p-nitroaniline (pNA) [ 23 ].…”

“…We have previously shown a significant increase in IL-1β gene expression in SPF chickens and DF-1 cells infected with virulent NDV strain [ 21 ]. Moreover, neutralizing IL-1β significantly reduced chicken morbidity and mortality, suggesting that NDV-induced inflammation plays a vital role in the pathogenesis of NDV infection and death [ 22 , 23 ]. Hence, it is necessary to clarify the mechanism underlying NDV-induced inflammation, to reduce the resultant inflammatory damage.…”

RNA sequencing reveals CircRNA expression profiles in chicken embryo fibroblasts infected with velogenic Newcastle disease virus

“…CEFs were infected with 1 MOI GM strain and harvested at indicated time points. The expression of NP protein was detected using western blot, as described previously ( 20 ).…”