| First Author | Liu G | Year | 2009 |
| Journal | J Immunol | Volume | 182 |
| Issue | 8 | Pages | 5063-71 |
| PubMed ID | 19342686 | Mgi Jnum | J:147490 |
| Mgi Id | MGI:3841304 | Doi | 10.4049/jimmunol.0803526 |
| Citation | Liu G, et al. (2009) p53 Attenuates lipopolysaccharide-induced NF-kappaB activation and acute lung injury. J Immunol 182(8):5063-71 |
| abstractText | The transcriptional factor p53 has primarily been characterized for its central role in the regulation of oncogenesis. A reciprocal relationship between the activities of p53 and NF-kappaB has been demonstrated in cancer cells, but there is little information concerning interactions between p53 and NF-kappaB in inflammatory processes. In this study, we found that neutrophils and macrophages lacking p53, i.e., p53(-/-), have elevated responses to LPS stimulation compared with p53(+/+) cells, producing greater amounts of proinflammatory cytokines, including TNF-alpha, IL-6, and MIP-2, and demonstrating enhanced NF-kappaB DNA-binding activity. p53(-/-) mice are more susceptible than are p53(+/+) mice to LPS-induced acute lung injury (ALI). The enhanced response of p53(-/-) cells to LPS does not involve alterations in intracellular signaling events associated with TLR4 engagement, such as activation of MAPKs, phosphorylation of IkappaB-alpha or the p65 subunit of NF-kappaB, or IkappaB-alpha degradation. Culture of LPS-stimulated neutrophils and macrophages with nutlin-3a, a specific inducer of p53 stabilization, attenuated NF-kappaB DNA-binding activity and production of proinflammatory cytokines. Treatment of mice with nutlin-3a reduced the severity of LPS-induced ALI. These data demonstrate that p53 regulates NF-kappaB activity in inflammatory cells and suggest that modulation of p53 may have potential therapeutic benefits in acute inflammatory conditions, such as ALI. |
