The Macrophage-Specific Transcription Factor Can Be Modified Posttranslationally by Ubiquitination in the Lipopolysaccharide-Treated Macrophages / 결핵및호흡기질환
Tuberculosis and Respiratory Diseases
; : 113-124, 2011.
Article
in En
| WPRIM
| ID: wpr-114366
Responsible library:
WPRO
ABSTRACT
BACKGROUND: Macrophages are one of the most important inflammatory cells in innate immunity. PU.1 is a macrophage-specific transcription factor. Ubiquitins are the ultimate regulator of eukaryotic transcription. The ubiquitination process for PU.1 is unknown. This study investigated the lipopolysaccharide (LPS)-induced activation of PU.1 and its relation to ubiquitins in the macrophages. METHODS: Raw264.7 cells, the primary cultured alveolar, pulmonary, and bone marrow derived macrophages were used. The Raw264.7 cells were treated with MG-132, NH4Cl, lactacytin and LPS. Nitric oxide and prostaglandin D2 and E2 were measured. Immunoprecipitation and Western blots were used to check ubiquitination of PU.1. RESULTS: The PU.1 ubiquitination increased after LPS (1 microg/mL) treatment for 4 hours on Raw264.7 cells. The ubiquitination of PU.1 by LPS was increased by MG-132 or NH4Cl pretreatment. Two hours of LPS treatment on macrophages, PU.1 activation was not induced nor increased with the inhibition of proteasomes and/or lysosomes. The ubiquitination of PU.1 was increased in LPS-treated Raw264.7 cells at 12- and at 24 hours. LPS-treated cells increased nitric oxide production, which was diminished by MG-132 or NH4Cl. LPS increased the production of PGE2 in the alveolar and peritoneal macrophages of wild type mice; however, PGE2 was blocked or diminished in Rac2 null mice. Pretreatment of lactacystin increased PGE2, however it decreased the PGD2 level in the macrophages derived from the bone marrow of B57/BL6 mice. CONCLUSION: LPS treatment in the macrophages ubiquitinates PU.1. Ubiquitination of PU.1 may be involved in synthesis of nitric oxide and prostaglandins.
Key words
Full text:
1
Index:
WPRIM
Main subject:
Acetylcysteine
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Transcription Factors
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Bone Marrow
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Ubiquitins
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Dinoprostone
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Prostaglandin D2
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Prostaglandins
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Blotting, Western
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Macrophages, Peritoneal
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Ubiquitin
Limits:
Animals
Language:
En
Journal:
Tuberculosis and Respiratory Diseases
Year:
2011
Type:
Article