CITED2 Restrains Proinflammatory Macrophage Activation and Response [Research Article]
Kim, G.-D., Das, R., Rao, X., Zhong, J., Deiuliis, J. A., Ramirez-Bergeron, D. L., Rajagopalan, S., Mahabeleshwar, G. H.
The American Society for Microbiology (ASM)
Published 2018
The American Society for Microbiology (ASM)
Published 2018
| Publication Date: |
2018-02-14
|
|---|---|
| Publisher: |
The American Society for Microbiology (ASM)
|
| Print ISSN: |
0270-7306
|
| Electronic ISSN: |
1098-5549
|
| Topics: |
Biology
Medicine
|
| Published by: |
| _version_ | 1836398792868364288 |
|---|---|
| autor | Kim, G.-D., Das, R., Rao, X., Zhong, J., Deiuliis, J. A., Ramirez-Bergeron, D. L., Rajagopalan, S., Mahabeleshwar, G. H. |
| beschreibung | Macrophages are strategically distributed in mammalian tissues and play an essential role in priming the immune response. However, macrophages need to constantly strike a balance between activation and inhibition states to avoid a futile inflammatory reaction. Here, we identify the CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2) as a potent repressor of macrophage proinflammatory activation. Gain- and loss-of-function studies revealed that CITED2 is required for optimal peroxisome proliferator-activated receptor gamma (PPAR) activation and attendant select anti-inflammatory gene expression in macrophages. More importantly, deficiency of CITED2 resulted in significant attenuation of rosiglitazone-induced PPAR activity, PPAR recruitment to target gene promoters, and anti-inflammatory target gene expression in macrophages. Interestingly, deficiency of Cited2 strikingly heightened proinflammatory gene expression through stabilization of hypoxia-inducible factor 1 alpha (HIF1α) protein in macrophages. Further, overexpression of Egln3 or inhibition of HIF1α in Cited2 -deficient macrophages completely reversed elevated proinflammatory cytokine/chemokine gene expression. Importantly, mice bearing a myeloid cell-specific deletion of Cited2 were highly susceptible to endotoxin-induced sepsis symptomatology and mortality. Collectively, our observations identify CITED2 as a novel negative regulator of macrophage proinflammatory activation that protects the host from inflammatory insults. |
| citation_standardnr | 6164435 |
| datenlieferant | ipn_articles |
| feed_id | 2374 |
| feed_publisher | The American Society for Microbiology (ASM) |
| feed_publisher_url | http://www.asm.org/ |
| insertion_date | 2018-02-14 |
| journaleissn | 1098-5549 |
| journalissn | 0270-7306 |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | The American Society for Microbiology (ASM) |
| quelle | Molecular and Cellular Biology |
| relation | http://mcb.asm.org/cgi/content/short/38/5/e00452-17?rss=1 |
| search_space | articles |
| shingle_author_1 | Kim, G.-D., Das, R., Rao, X., Zhong, J., Deiuliis, J. A., Ramirez-Bergeron, D. L., Rajagopalan, S., Mahabeleshwar, G. H. |
| shingle_author_2 | Kim, G.-D., Das, R., Rao, X., Zhong, J., Deiuliis, J. A., Ramirez-Bergeron, D. L., Rajagopalan, S., Mahabeleshwar, G. H. |
| shingle_author_3 | Kim, G.-D., Das, R., Rao, X., Zhong, J., Deiuliis, J. A., Ramirez-Bergeron, D. L., Rajagopalan, S., Mahabeleshwar, G. H. |
| shingle_author_4 | Kim, G.-D., Das, R., Rao, X., Zhong, J., Deiuliis, J. A., Ramirez-Bergeron, D. L., Rajagopalan, S., Mahabeleshwar, G. H. |
| shingle_catch_all_1 | CITED2 Restrains Proinflammatory Macrophage Activation and Response [Research Article] Macrophages are strategically distributed in mammalian tissues and play an essential role in priming the immune response. However, macrophages need to constantly strike a balance between activation and inhibition states to avoid a futile inflammatory reaction. Here, we identify the CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2) as a potent repressor of macrophage proinflammatory activation. Gain- and loss-of-function studies revealed that CITED2 is required for optimal peroxisome proliferator-activated receptor gamma (PPAR) activation and attendant select anti-inflammatory gene expression in macrophages. More importantly, deficiency of CITED2 resulted in significant attenuation of rosiglitazone-induced PPAR activity, PPAR recruitment to target gene promoters, and anti-inflammatory target gene expression in macrophages. Interestingly, deficiency of Cited2 strikingly heightened proinflammatory gene expression through stabilization of hypoxia-inducible factor 1 alpha (HIF1α) protein in macrophages. Further, overexpression of Egln3 or inhibition of HIF1α in Cited2 -deficient macrophages completely reversed elevated proinflammatory cytokine/chemokine gene expression. Importantly, mice bearing a myeloid cell-specific deletion of Cited2 were highly susceptible to endotoxin-induced sepsis symptomatology and mortality. Collectively, our observations identify CITED2 as a novel negative regulator of macrophage proinflammatory activation that protects the host from inflammatory insults. Kim, G.-D., Das, R., Rao, X., Zhong, J., Deiuliis, J. A., Ramirez-Bergeron, D. L., Rajagopalan, S., Mahabeleshwar, G. H. The American Society for Microbiology (ASM) 0270-7306 02707306 1098-5549 10985549 |
| shingle_catch_all_2 | CITED2 Restrains Proinflammatory Macrophage Activation and Response [Research Article] Macrophages are strategically distributed in mammalian tissues and play an essential role in priming the immune response. However, macrophages need to constantly strike a balance between activation and inhibition states to avoid a futile inflammatory reaction. Here, we identify the CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2) as a potent repressor of macrophage proinflammatory activation. Gain- and loss-of-function studies revealed that CITED2 is required for optimal peroxisome proliferator-activated receptor gamma (PPAR) activation and attendant select anti-inflammatory gene expression in macrophages. More importantly, deficiency of CITED2 resulted in significant attenuation of rosiglitazone-induced PPAR activity, PPAR recruitment to target gene promoters, and anti-inflammatory target gene expression in macrophages. Interestingly, deficiency of Cited2 strikingly heightened proinflammatory gene expression through stabilization of hypoxia-inducible factor 1 alpha (HIF1α) protein in macrophages. Further, overexpression of Egln3 or inhibition of HIF1α in Cited2 -deficient macrophages completely reversed elevated proinflammatory cytokine/chemokine gene expression. Importantly, mice bearing a myeloid cell-specific deletion of Cited2 were highly susceptible to endotoxin-induced sepsis symptomatology and mortality. Collectively, our observations identify CITED2 as a novel negative regulator of macrophage proinflammatory activation that protects the host from inflammatory insults. Kim, G.-D., Das, R., Rao, X., Zhong, J., Deiuliis, J. A., Ramirez-Bergeron, D. L., Rajagopalan, S., Mahabeleshwar, G. H. The American Society for Microbiology (ASM) 0270-7306 02707306 1098-5549 10985549 |
| shingle_catch_all_3 | CITED2 Restrains Proinflammatory Macrophage Activation and Response [Research Article] Macrophages are strategically distributed in mammalian tissues and play an essential role in priming the immune response. However, macrophages need to constantly strike a balance between activation and inhibition states to avoid a futile inflammatory reaction. Here, we identify the CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2) as a potent repressor of macrophage proinflammatory activation. Gain- and loss-of-function studies revealed that CITED2 is required for optimal peroxisome proliferator-activated receptor gamma (PPAR) activation and attendant select anti-inflammatory gene expression in macrophages. More importantly, deficiency of CITED2 resulted in significant attenuation of rosiglitazone-induced PPAR activity, PPAR recruitment to target gene promoters, and anti-inflammatory target gene expression in macrophages. Interestingly, deficiency of Cited2 strikingly heightened proinflammatory gene expression through stabilization of hypoxia-inducible factor 1 alpha (HIF1α) protein in macrophages. Further, overexpression of Egln3 or inhibition of HIF1α in Cited2 -deficient macrophages completely reversed elevated proinflammatory cytokine/chemokine gene expression. Importantly, mice bearing a myeloid cell-specific deletion of Cited2 were highly susceptible to endotoxin-induced sepsis symptomatology and mortality. Collectively, our observations identify CITED2 as a novel negative regulator of macrophage proinflammatory activation that protects the host from inflammatory insults. Kim, G.-D., Das, R., Rao, X., Zhong, J., Deiuliis, J. A., Ramirez-Bergeron, D. L., Rajagopalan, S., Mahabeleshwar, G. H. The American Society for Microbiology (ASM) 0270-7306 02707306 1098-5549 10985549 |
| shingle_catch_all_4 | CITED2 Restrains Proinflammatory Macrophage Activation and Response [Research Article] Macrophages are strategically distributed in mammalian tissues and play an essential role in priming the immune response. However, macrophages need to constantly strike a balance between activation and inhibition states to avoid a futile inflammatory reaction. Here, we identify the CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2) as a potent repressor of macrophage proinflammatory activation. Gain- and loss-of-function studies revealed that CITED2 is required for optimal peroxisome proliferator-activated receptor gamma (PPAR) activation and attendant select anti-inflammatory gene expression in macrophages. More importantly, deficiency of CITED2 resulted in significant attenuation of rosiglitazone-induced PPAR activity, PPAR recruitment to target gene promoters, and anti-inflammatory target gene expression in macrophages. Interestingly, deficiency of Cited2 strikingly heightened proinflammatory gene expression through stabilization of hypoxia-inducible factor 1 alpha (HIF1α) protein in macrophages. Further, overexpression of Egln3 or inhibition of HIF1α in Cited2 -deficient macrophages completely reversed elevated proinflammatory cytokine/chemokine gene expression. Importantly, mice bearing a myeloid cell-specific deletion of Cited2 were highly susceptible to endotoxin-induced sepsis symptomatology and mortality. Collectively, our observations identify CITED2 as a novel negative regulator of macrophage proinflammatory activation that protects the host from inflammatory insults. Kim, G.-D., Das, R., Rao, X., Zhong, J., Deiuliis, J. A., Ramirez-Bergeron, D. L., Rajagopalan, S., Mahabeleshwar, G. H. The American Society for Microbiology (ASM) 0270-7306 02707306 1098-5549 10985549 |
| shingle_title_1 | CITED2 Restrains Proinflammatory Macrophage Activation and Response [Research Article] |
| shingle_title_2 | CITED2 Restrains Proinflammatory Macrophage Activation and Response [Research Article] |
| shingle_title_3 | CITED2 Restrains Proinflammatory Macrophage Activation and Response [Research Article] |
| shingle_title_4 | CITED2 Restrains Proinflammatory Macrophage Activation and Response [Research Article] |
| timestamp | 2025-06-30T23:32:42.579Z |
| titel | CITED2 Restrains Proinflammatory Macrophage Activation and Response [Research Article] |
| titel_suche | CITED2 Restrains Proinflammatory Macrophage Activation and Response [Research Article] |
| topic | W WW-YZ |
| uid | ipn_articles_6164435 |