SPLUNC1蛋白抑制猪肺炎支原体诱导促炎因子表达的机制研究

Mycoplasma hyopneumoniae (Mhp) is the etiologic agent of mycoplasma pneumonia(Mps). It could cause chronic inflammation of lung tissue, and trigger secondary infections. Airway epithelial cells was regarded as the first line in the host defense against microorganisms. Short Palate Lung and Nasal epithelium Clone l (SPLUNC1) is one of the most highly expressed secretory protein with important antimicrobial and anti-inflammatory functions. However, the role of SPLUNC1 in Mhp infection was not clear. In this study, we have demonstrated that SPLUNC1 inhibited the Mhp-induced production of pro-inflammatory cytokines IL-1beta and TNF-alpha, but the mechanism was not clear. Therefore, this study will analyze the expression rule of SPLUNC1 induced by Mhp infection, and its relationship with the Mhp-induced production of pro-inflammatory cytokines. Then, we will determine the effects of SPLUNC1 on Mhp growth and infection, and Mhp lipidassociated membrane proteins (LAMPS) or TLR2/6 agonists activiated-inflammatory signaling pathway. Finally, this study will comprehensively elucidate the molecular mechanism of SPLUNC1 in suppressing the expression of Mhp-induced pro-inflammatory cytokines, and provide a new theoretical basis for the prevention and control of Mhp.

猪肺炎支原体(Mhp)是猪支原体肺炎(Mps)的主要病原，可引起肺脏的慢性炎症并引发其他病原继发感染。呼吸道上皮是宿主抵抗病原入侵的首要防线，而短的上腭、肺及鼻咽上皮克隆1蛋白(SPLUNC1)是其分泌的含量最高且具有重要抗菌和抗炎功能的蛋白，但该蛋白在Mhp感染过程中的作用尚不明确。我们前期研究发现，SPLUNC1可抑制Mhp感染引起的促炎因子IL-1beta和TNF-alpha的表达，但其机制不明。因此，本项目拟解析Mhp感染诱导SPLUNC1产生的规律及其与促炎因子表达的关系，明确SPLUNC1对Mhp生长感染的作用，阐明其对Mhp膜脂蛋白或TLR2/6激动剂引起的炎性通路活化的影响，系统揭示SPLUNC1抑制Mhp诱导促炎因子表达的分子机制，为Mhp的预防和控制提供新的理论依据。

猪肺炎支原体(Mhp)是猪支原体肺炎(Mps)的主要病原，可引起肺脏的慢性炎症并引发其他病原继发感染。呼吸道上皮是宿主抵抗病原入侵的首要防线，而短的上腭、肺及鼻咽上皮克隆1蛋白(SPLUNC1)是其分泌的含量最高且具有重要抗菌和抗炎功能的蛋白，但该蛋白在Mhp感染过程中的作用尚不明确。本项目阐明了Mhp调控SPLUNC1以及促炎因子表达变化的规律；明确了SPLUNC1可抑制Mhp感染引起的促炎性因子表达的上调；发现SPLUNC1对Mhp生长和黏附无显著的影响；揭示了SPLUNC1可通过抑制MAPK信号通路的活化来抑制促炎性因子表达的上调。以上研究为Mhp的预防和控制提供新的理论依据。