Xiangbin Xu, Chang-Hoon Woo, Steere, Rachel R., Lee, Byung Cheol, Yuxian Huang, Jing Wu, Jinjiang Pang, Jae Hyang Lim, Haidong Xu, Wenhong Zhang, Konduru, Anuhya S., Chen Yan, Cheeseman, Michael T., Brown, Steve D. M., and Jian-Dong Li
Inflammation is a hallmark of many important human diseases. Appropriate inflammation is critical for host defense; however, an overactive response is detrimental to the host. Thus, inflammation must be tightly regulated. The molecular mechanisms underlying the tight regulation of inflammation remain largely unknown. Ecotropic viral integration site 1 (EVIl), a proto-oncogene and zinc finger transcription factor, plays important roles in normal development and leukemogenesis. However, its role in regulating NF-κB-dependent inflammation remains unknown. In this article, we show that EVIl negatively regulates nontypeable Haemophilus influenzae- and TNF-α-induced NF-κB-dependent inflammation in vitro and in vivo. EVIl directly binds to the NF-kappa;B p65 subunit and inhibits its acetylation at lysine 310, thereby inhibiting its DNA-binding activity. Moreover, expression of EVIl itself is induced by nontypeable Haemophilus influenzae and TNF-α in an NF-κB-dependent manner, thereby unveiling a novel inducible negative feedback loop to tightly control NF-&B-dependent inflammation. Thus, our study provides important insights into the novel role for EVIl in negatively regulating NF-κB-dependent inflammation, and it may also shed light on the future development of novel anti-inflammatory strategies. [ABSTRACT FROM AUTHOR]