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

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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.