Role of preprotachykinin-A gene products on multiple organ injury in LPS-induced endotoxemia
In: Journal of Leukocyte Biology, Jg. 83 (2007-11-12), S. 288-295
Online
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Zugriff:
Endotoxemia is a life-threatening, inflammatory condition that involves multiple organ injury and dysfunction. Preprotachykinin-A (PPT-A) gene products, substance P (SP), and neurokinin-A have been shown to play an important role in neurogenic inflammation. To investigate the role of PPT-A gene products on multiple organ injury in LPS-induced endotoxemia, endotoxemia was induced by LPS administration (10 mg/kg, i.p.) in PPT-A gene-deficient mice (PPTA−/−) and the wild-type (WT) control mice (PPT-A+/+). I.p. administration of LPS to WT mice caused a significant increase in circulating levels of SP as well as in liver, lung, and kidney. PPT-A gene deletion significantly protected against liver, pulmonary, and renal injury following LPS-induced endotoxemia, as evidenced by tissue myeloperoxidase activities, plasma alanine aminotransferase, aspartate aminotransferase levels, and histological examination. Furthermore, PPT-A−/− mice had significantly attenuated chemokines, proinflammatory cytokines, and adhesion molecule levels in the liver, lung, and kidney. These results show that PPT-A gene products are critical proinflammatory mediators in endotoxemia and the associated multiple organ injury. In addition, the data suggest that deletion of the PPT-A gene protected mice against organ damage in endotoxemia by disruption in neutrophil recruitment.
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Role of preprotachykinin-A gene products on multiple organ injury in LPS-induced endotoxemia
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Autor/in / Beteiligte Person: | Zhang, Huili ; Siaw Wei Ng ; Hegde, Akhil ; Bhatia, Madhav |
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Zeitschrift: | Journal of Leukocyte Biology, Jg. 83 (2007-11-12), S. 288-295 |
Veröffentlichung: | Oxford University Press (OUP), 2007 |
Medientyp: | unknown |
ISSN: | 1938-3673 (print) ; 0741-5400 (print) |
DOI: | 10.1189/jlb.0807575 |
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