Functional analysis of tissue inhibitor of metalloproteinase-1 (TIMP-1) after influenza A virus infection

基质金属蛋白酶（MMPs）及其抑制剂在炎症反应和生理性组织重塑中起着重要的调节作用。我们发现，甲型流感病毒（IAV）感染后，肺组织金属蛋白酶-1 （TIMP-1）的表达被显著诱导，TIMP-1是MMPs的特异性抑制剂。因此，我们重点研究了TIMP-1在发病机制中的功能，并用该病毒感染TIMP-1 KO和野生型（WT）小鼠。IAV感染后，TIMP-1 KO小鼠的存活率低于WT小鼠。此外，在感染后7天，TIMP-1 KO小鼠支气管肺泡灌洗液（BALF）中检测到严重的出血倾向，TIMP-1 KO小鼠BALF中的炎症细胞积累比WT小鼠增加。因此，我们认为TIMP-1参与了对肺部过度炎症反应的保护。

Matrix metalloproteinases (MMPs) and their inhibitors play an important regulatory role in the inflammatory responses and physiologic tissue remodeling. We found that the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), which is a specific inhibitor of MMPs, was remarkably induced in the lungs after influenza A virus (IAV) infection. Therefore, we focused on the function of TIMP-1 for the pathogenesis, and infected TIMP-1 KO and wild type (WT) mice with the virus. After IAV infection, the survival rate of TIMP-1 KO mice was lower than that of WT mice. In addition, at 7 day after the infection, severe hemorrhagic tendency was detected in the bronchoalveolar lavage fluid (BALF) in TIMP-1 KO mice, and inflammatory cell accumulation in BALF increased in TIMP-1 KO mice, compared with WT mice. Therefore, it was suggested that TIMP-1 is involved in the protection of the lung against excessive inflammatory response.