Unknown

Dataset Information

0

Histone deacetylase 2 is essential for LPS-induced inflammatory responses in macrophages.


ABSTRACT: The role of specific histone deacetylase (HDAC) proteins in regulating the lipopolysaccharide (LPS)-induced inflammatory response and its underlying mechanisms are unclear. Here, HDAC2, a class I HDAC family protein, is essential for the LPS-triggered inflammatory response in macrophages. LPS stimulation increases HDAC2 expression in macrophages. Knockdown of HDAC2 decreases the expression of proinflammatory genes, such as IL-12, TNF-? and iNOS following stimulation with LPS. The adoptive transfer of HDAC2 knockdown macrophages attenuates the LPS-triggered innate inflammatory response in vivo, and these mice are less sensitive to endotoxin shock and Escherichia coli-induced sepsis. Mechanistically, the c-Jun protein is the main target of HDAC2-mediated LPS-induced production of proinflammatory cytokines. Moreover, HDAC2 knockdown increases the expression of c-Jun, which directly binds the promoters of proinflammatory genes and forms nuclear receptor corepressor complexes to inhibit the transcription of proinflammatory genes in macrophages. These effects are rescued by c-Jun expression. According to the chromatin immunoprecipitation analysis, HDAC2 also selectively suppresses c-Jun expression by directly binding to its promoter and modifying histone acetylation after LPS stimulation. Our findings define a new function and mechanism of the HDAC2/c-Jun signaling network that regulates the LPS-induced immune response in macrophages.

SUBMITTER: Wu C 

PROVIDER: S-EPMC7379312 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

Histone deacetylase 2 is essential for LPS-induced inflammatory responses in macrophages.

Wu Chenming C   Li Ang A   Hu Jian J   Kang Jiuhong J  

Immunology and cell biology 20181031 1


The role of specific histone deacetylase (HDAC) proteins in regulating the lipopolysaccharide (LPS)-induced inflammatory response and its underlying mechanisms are unclear. Here, HDAC2, a class I HDAC family protein, is essential for the LPS-triggered inflammatory response in macrophages. LPS stimulation increases HDAC2 expression in macrophages. Knockdown of HDAC2 decreases the expression of proinflammatory genes, such as IL-12, TNF-α and iNOS following stimulation with LPS. The adoptive transf  ...[more]

Similar Datasets

| S-EPMC7412499 | biostudies-literature
| S-EPMC7196186 | biostudies-literature
| S-EPMC6917034 | biostudies-literature
| S-EPMC8512965 | biostudies-literature
| S-EPMC6472047 | biostudies-literature
| S-EPMC3479529 | biostudies-literature
| S-EPMC5183739 | biostudies-literature
| S-EPMC8094043 | biostudies-literature
| S-SCDT-10_15252-EMBJ_2022111867 | biostudies-other
| S-EPMC5733936 | biostudies-literature