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KMID : 0383820110700020113
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Tuberculosis and Respiratory Diseases
2011 Volume.70 No. 2 p.113 ~ p.124
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The Macrophage-Specific Transcription Factor Can Be Modified
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Jung Jae-Woo
Choi Jae-Chol
Kim Jae-Yeol
Park In-Won
Choi Byoung-Whui
Shin Jong-Wook
John William Christman
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Abstract
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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 (1μg/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.
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KEYWORD
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Macrophages, PU.1, ubiquitin, Proteasome, Lysosomes
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