Preprotachykinin-A gene products are key mediators of lung injury in polymicrobial sepsis |
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Authors: | Puneet Padmam Hegde Akhil Ng Siaw Wei Lau Hon Yen Lu Jia Moochhala Shabbir M Bhatia Madhav |
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Institution: | Department of Pharmacology, National University of Singapore, 18 Medical Drive, Singapore 117597. |
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Abstract: | Preprotachykinin-A (PPT-A) gene products substance P and neurokinin-A have been shown to play an important role in neurogenic inflammation. To investigate the role of PPT-A gene products in lung injury in sepsis, polymicrobial sepsis was induced by cecal ligation and puncture in PPT-A gene-deficient mice (PPT-A(-/-)) and the wild-type control mice (PPT-A(+/+)). PPT-A gene deletion significantly protected against mortality, delayed the onset of lethality, and improved the long-term survival following cecal ligation and puncture-induced sepsis. PPT-A(-/-) mice also had significantly attenuated inflammation and damage in the lungs. The data suggest that deletion of the PPT-A gene may have contributed to the disruption in recruitment of inflammatory cells resulting in protection against tissue damage, as in these mice the sepsis-associated increase in chemokine levels is significantly attenuated. |
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