Citation
Kim SJ, Varghese TK, Zhang Z, Zhao LC, Thomas G, Hummel M, Abecassis M. Renal ischemia/reperfusion injury activates the enhancer domain of the human cytomegalovirus major immediate early promoter. Am J Transplant. 2005; 5;1606-13.
Abstract
Reactivation of latent human cytomegalovirus is of significant concern in immunocompromised transplant patients and is likely to occur through transcriptional activation of immediate early (ie) gene expression through mechanisms that are not well understood. TNF-mediated activation of NF-kappaB has been proposed to be one pathway leading to transcriptional activation of CMV ie gene expression. Using transgenic mice carrying a lacZ reporter gene under the control of the HCMV major ie promoter/enhancer (MIEP-lacZ mice) and MIEP-lacZ mice deficient in TNF receptor 1 and TNF receptor 2 (MIEP-lac Z TNFR DKO mice), we demonstrate that renal ischemia/reperfusion (I/R) injury activates the HCMV enhancer independently of TNF. Induction of MIEP-lacZ expression was preceded by TNFR-independent formation of reactive oxygen species (ROS), weak and transient activation of NF-kappaB and strong and sustained activation of AP-1. Our studies show that, in addition to TNF-mediated signaling, TNF-independent signaling induced by I/R injury can contribute to the activation of the HCMV enhancer. This likely occurs through ROS-mediated activation of AP-1. Targeting MAP kinase signaling pathways as well as NF-kappaB may be of therapeutic value in patients with CMV infection.
Key Points
- Published in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons in 2005.
- Indexed in PubMed as PMID 15943618.
- Mapped to Uro-Oncology, Trauma & Fistula, Stones & BPH.
- Abstract available from PubMed and rendered as static text on this page.
Clinical Relevance
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