| First Author | Ng SW | Year | 2008 |
| Journal | J Leukoc Biol | Volume | 83 |
| Issue | 2 | Pages | 288-95 |
| PubMed ID | 17998302 | Mgi Jnum | J:131213 |
| Mgi Id | MGI:3773360 | Doi | 10.1189/jlb.0807575 |
| Citation | Ng SW, et al. (2008) Role of preprotachykinin-A gene products on multiple organ injury in LPS-induced endotoxemia. J Leukoc Biol 83(2):288-95 |
| abstractText | 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. |
