In:
The Journal of Immunology, The American Association of Immunologists, Vol. 188, No. 12 ( 2012-06-15), p. 6371-6380
Kurzfassung:
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 (EVI1), 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 EVI1 negatively regulates nontypeable Haemophilus influenzae- and TNF-α–induced NF-κB–dependent inflammation in vitro and in vivo. EVI1 directly binds to the NF-κB p65 subunit and inhibits its acetylation at lysine 310, thereby inhibiting its DNA-binding activity. Moreover, expression of EVI1 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-κB–dependent inflammation. Thus, our study provides important insights into the novel role for EVI1 in negatively regulating NF-κB–dependent inflammation, and it may also shed light on the future development of novel anti-inflammatory strategies.
Materialart:
Online-Ressource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.1103527
Sprache:
Englisch
Verlag:
The American Association of Immunologists
Publikationsdatum:
2012
ZDB Id:
1475085-5
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