The Role Of SOCS3 In Acute Lung Injury And Secondary Bacterial Pneumonia Caused By H9N2-AIV Infection

Although H9N2 avian influenza virus (H9N2-AIV) belong to low pathogenic avian influenza virus (LPAIV), it attracted more and more attention of scientists in recent years for the characteristics of broad host range, widespread epidemic, genetic recombinant, as well as being able to provide internal gene segments for other subtypes of influenza A virus (such as H5N1、H7N9 and H10N8). Acute lung injury (ALI) and secondary bacterial pneumonia induced by AIV are key elements that lead to human death. For example, the mortality of human infected with H7N9 or H5N1 exceed 30%, notably,90% of deaths were complicated by secondary bacterial pneumonia. Suppressor of cytokines signaling 3 (SOCS3) was an important negative regulatory protein during the immune inflammatory response,which was regarded as an inhibitor of excessive inflammatory response induced by ALI. However, the role of SOCS3 in ALI and secondary bacterial pneumonia induced by H9N2-AIV was still unclear. Based on this, we firstly constructed a recombinant plasmid SOCS3-pCDNA3.1 and SOCS3-shRNA lentivirus plasmid to evaluate the role of SOCS3 in ALI in vitro. Subsequently, we developed a mouse model to investigate the role of SOCS3 in secondary bacterial pneumonia after H9N2-AIV infection. The results indicated that SOCS3 has obvious inhibitory effect on pro-inflammatory factors TNF-α, IL-6 and the nuclear factor kB (NF-kB) induced by H9N2-AIV in vitro. The recombinant plasmid SOCS3-pCDNA3.1 was delivered into the BALB/c female mice through intraperitoneal injection, which could decrease the expression level of TNF-α, IL-6 and NF-kB. However, the decreased levels of these cytokines could not contribute to the attenuation of pulmonary edema and lung injury.In conclusion, SOCS3 plays a crucial role in H9N2-AIV induced ALI and secondary bacterial pneumonia. This study may provide a therapeutic potential for the treatment of ALI and secondary lung injury, and also may hold some scientific basis to clinic treatment.