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SREBP‐1a Regulates Cellular Defense Responses in Bone Marrow‐Derived Macrophages
Author(s) -
Im SeungSoon,
Hammond Linda E,
Yousef Leyla,
Fraser Deborah,
Tenner Andrea J,
Young Steven,
Osborne Timothy F
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.273
Subject(s) - sterol regulatory element binding protein , microbiology and biotechnology , biology , phagocytosis , immune system , gene knockdown , innate immune system , macrophage , haematopoiesis , cell culture , apoptosis , gene expression , immunology , gene , stem cell , in vitro , biochemistry , genetics
Macrophages are highly specialized cells with major functions in the innate immune system. They are critical accessory cells that are important in the defense against invading pathogens. Sterol response element binding protein (SREBP)‐1a is a key transcriptional regulator of lipogenesis and cell growth and its' properly regulated activity is key to cellular lipid homeostasis. In a recent report, the event of cellular attack by a bacterial α‐toxin showed that SREBP activated lipogenic gene expression to presumably provide lipid for repairing the membrane damage caused by the toxin. But these studies were performed in established cultured cell lines. Moreover, a functional role for SREBP‐1a in macrophages has not been addressed. We established a line of mice that resulted in a greater than 95% knockdown in SREBP‐1a mRNA in every tissue examined using a β‐geo “gene trap”system. In this study, we show that macrophages from these SREBP‐1a knock out (1aKO) mice undergo increased apoptosis in response to bacterial α‐toxin treatment. Additionally, the 1aKO macrophages exhibited a significant decrease in phagocytosis of sheep red blood cells as compared to macrophages isolated from wild type (WT) control mice. These observations indicate that SREBP‐1a may play a key role in macrophage cell function and protection against pathogen exposure. NIH/NHLB1 (RO1 HL48044), MOEHRD (KRF‐2006‐352‐E00005)