Critical role of type 1 plasminogen activator inhibitor (PAI-1) in early host defense against nontypeable Haemophilus influenzae (NTHi) infection

Title
Critical role of type 1 plasminogen activator inhibitor (PAI-1) in early host defense against nontypeable Haemophilus influenzae (NTHi) infection
Author(s)
임재향[임재향]우창훈젠동리[젠동리]
Keywords
TOLL-LIKE RECEPTORS; ACUTE LUNG INJURY; MUCIN TRANSCRIPTION; NEGATIVE REGULATOR; IMMUNE-RESPONSE; CROSS-TALK; INNATE; INFLAMMATION; PNEUMONIA; CYLD
Issue Date
201110
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Citation
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.414, no.1, pp.67 - 72
Abstract
Respiratory systems are constantly being challenged by pathogens. Lung epithelial cells serve as a first line of defense against microbial pathogens by detecting pathogen-associated molecular patterns (PAMPs) and activating downstream signaling pathways, leading to a plethora of biological responses required for shaping both the innate and adaptive arms of the immune response. Acute-phase proteins (APPs), such as type 1 plasminogen activator inhibitor (PAL-1), play important roles in immune/inflammatory responses. PAI-1, a key regulator for fibrinolysis and coagulation, acts as an APP during acute phase response (APR) such as acute lung injury (ALI), inflammation, and sepsis. However, the role of PAL-1 in the pathogenesis of these diseases still remains unclear, especially in bacterial pneumonia. In this study, we showed that PAL-1 expression is upregulated following nontypeable Haemophilus influenzae (NTHi) infection. PAL-1 knockout (KO) mice failed to generate early immune responses against NTHi. Failure of generating early immune responses in PAI-1 KO mice resulted in reduced bacterial clearance and prolonged disease process, which in turn led to enhanced inflammation at late stage of infection. Moreover, we also found that NTHi induces PAL-1 via activation of TLR2-MyD88-MKK3-p38 MAPK signaling pathway. These data suggest that PAL-1 plays critical role in earl host defense response against NTHi infection. Our study thus reveals a novel role of PAI-1 in infection caused by NTHi, one of the most common gram-negative bacterial pathogens in respiratory systems. (C) 2011 Elsevier Inc. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/24389http://dx.doi.org/10.1016/j.bbrc.2011.09.023
ISSN
0006-291X
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의과대학 > 약리학교실 > Articles
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