| Influenza A virus(IAV)causes millions of severe cases and 0.25-0.50 million deaths every year.Patients infected with influenza virus often suffer from aggressive proinflammatory response and aberrant anti-inflammatory response,manifested as cytokines redundancy.We usually call this Cytokine storm.Cytokine storm is a kind of excessive innate immune response and always leads infection to serious injury or death.JAK-STAT pathway is a cytokine receptor related signal transduction pathway.The suppressor in the cytokine signaling(SOCS)proteins are a kind of negative feedback inhibitory proteins of JAK-STAT pathway.The SOCS proteins may be related to the formation of cytokine storm but the mechanism is still not clear.In this study,we found that IAV increased the expression of IL-6 and SOCS3 in A549 cells,RAW264.7 cells and C57BL/6 mice.Especially at the early stage of IAV infection,SOCS3 expression was significantly increased in mouse lung tissue,indicating that the expression of SOCS3 may be involved in the early stage of cytokine storm formation.Interestingly,our result showed that the expression of SOCS3 in A549 cells was not induced by the cell culture supernatants collected at 3 hours postinfection,suggesting that the IAV-induced early expression of SOCS3 was not dependent on cytokines.Furthermore,we found that the expression of SOCS3 did not change in type I interferon receptor knockout mouse lung as compared with that in wild type mouse lung,indicating that SOCS3 early expression was not dependent on the type I interferon.Moreover,we observed that the shRNA-based knockdown of SOCS3 in RAW264.7 cells could significantly downregulate the expression of IL-6,TNF-α and IL-10 after IAV infection.Therefore,IAV infection maybe induce robust SOCS3 expression that inhibits the JAK-STAT pathway and its downstream signals,resulting in the compensatory increase the expressions of IL-6,TNF-α and IL-10.Our findings provide a new view of the cytokine storm formation during IAV infection. |
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