The phosphatase and tensin homolog PTEN improves murine polymicrobial sepsis outcome by decreasing MyD88 expression. (P1344)
| Autor: | Flavia Sisti, Ana Ferreira, Suojuan Wang, Luciano Filgueiras, Zhuo Wang, Fernando Cunha, Jose Alves-Filho, C. Henrique Serezani |
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| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 190:207.1-207.1 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Sepsis is systemic inflammatory response caused by an infectious agent and may progress to multiple organ dysfunction and death. Therapeutic strategies to inhibit excessive inflammation in sepsis are needed. The lipid and protein phosphatase PTEN is a well-known tumor suppressor, but its role in host defense is poorly studied. Here, we investigated whether PTEN activation is involved in TLR activation in vivo and in vitro. PTEN expression is decreased in cells from the peritoneal cavity 24 h after cecum ligation and puncture (CLP). In vivo pretreatment with the PTEN inhibitor bpV(HOpic) 150 ug/Kg for 1 hour before cecum and ligation puncture decreases animals survival, associated with high bacterial number in the peritoneal cavity when compared to untreated mice. In vivo PTEN inhibition increases expression of the TLR adaptor MyD88 during sepsis. In vitro, LPS (TLR4) and PAM3Cys (TLR2) increase PTEN phosphorylation in thyoglicolate-elicited macrophages (MΦs). PTEN mRNA silencing further enhances MyD88 expression and TLR-2 and -4-induced IRAK and NFkB p65 phosphorylation. Transfection of MΦs with adenovirus expressing constitutively active PTEN decreases MyD88 expression. Together, our data show that PTEN is a key determinant of macrophage TLR activation by decreasing MyD88 expression, leading to reduced systemic inflammatory response and therefore improving sepsis outcome. |
| Databáze: | OpenAIRE |
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