Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/99923
Title: A novel serine protease inhibitor acts as an immunomodulatory switch while maintaining homeostasis
Authors: Jiang, N. 
Thangamani, S. 
Chor, C.F.
Wang, S.Y.
Winarsih, I. 
Du, R.J. 
Sivaraman, J. 
Ho, B.
Ding, J.L. 
Keywords: Homeostasis
Immunomodulation
Kinetic profiles
Prophenoloxidase pathway
Serine protease inhibitor
Serine proteases
Issue Date: Jul-2009
Citation: Jiang, N., Thangamani, S., Chor, C.F., Wang, S.Y., Winarsih, I., Du, R.J., Sivaraman, J., Ho, B., Ding, J.L. (2009-07). A novel serine protease inhibitor acts as an immunomodulatory switch while maintaining homeostasis. Journal of Innate Immunity 1 (5) : 465-479. ScholarBank@NUS Repository.
Abstract: Serine protease cascades boost immune responses while maintaining homeostasis. These crucial actions are intricately regulated by cognate serine protease inhibitors. However, the mechanism underlying such a dynamic immunomodulation during acute phase infection remains obscure, particularly where the pathogen's serine protease adds a new challenge to the host. Here, we found that infection of horseshoe crab, Carcinoscorpius rotundicauda, induced reciprocal profiles of CrSPI (serine protease inhibitor) and CrFurin (serine protease) with respect to their transcription and protein activities. Using recombinant rCrSPI, we explored its inhibitory activity against various microbial proteases and found it most efficacious against a model serine protease, subtilisin A. rCrSPI inhibited subtilisin at Ki 10-9M with a molar ratio of 1 rCrSPI:2 subtilisin. The rCrSPI also inhibited plasma CrFurin, suppressed subtilisin-mediated activation of prophenoloxidase (PPO) and interacted with complement C3. Taken together, CrSPI acts as a key immunomodulatory 'on-off' switch in a 2-way regulation of serine protease microbial subtilisin and host serine proteases (CrFurin and CrC3), thereby controlling immune responses involving the complements and the PPO-mediated antimicrobial activities, while maintaining homeostasis. Copyright © 2009 S. Karger AG.
Source Title: Journal of Innate Immunity
URI: http://scholarbank.nus.edu.sg/handle/10635/99923
ISSN: 1662811X
Appears in Collections:Staff Publications

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