Phospholipase D2 acts as an important regulator in LPS-induced nitric oxide synthesis in Raw 264.7 cells |
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| Authors: | Shin-Young Park Ju Hwan Cho Weina Ma Hye-Jin Choi Joong-Soo Han |
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| Institution: | 1. Department of Genitourinary Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China;2. Key Laboratory of Cancer Prevention and Therapy, Tianjin, China;3. Department of Gynecology, Cangzhou Central Hospital, Hebei Medical University, Cangzhou, China;4. Institute of Bioengineering and Nanotechnology, Singapore;3. Department of Immunology, St. Jude Children''s Research Hospital, Memphis, Tennessee 38105-3678,;4. Department of Biological Sciences, University of Memphis, Memphis, Tennessee 38152,;5. Department of Veterinary Physiology and Biochemistry, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar 125004, Haryana, India,;6. Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom,;9. Departments ofBiochemistry, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6600,;8. Department of Chemistry and The Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37232, and;12. Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, Tennessee 37232-0697;1. Department of Oral Biology, Faculty of Odontology, Malmö University College, Malmö, Sweden;2. Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, Free University and University of Amsterdam, Amsterdam, The Netherlands;3. Department of Biochemistry and Molecular Biology, Wright State University School Medicine, Dayton, Ohio 45435 and;4. Department of Food Science, Rutgers Center for Lipid Research, and New Jersey Institute for Food, Nutrition, and Health, Rutgers University, New Brunswick, New Jersey 08901;1. Department of Biochemistry and Molecular Biology, Wright State University School of Medicine, Dayton, Ohio 45435 |
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| Abstract: | The purpose of this study was to identify the role of phospholipase D2 (PLD2) in lipopolysaccharide (LPS)-induced nitric oxide (NO) synthesis. LPS enhanced NO synthesis and inducible nitric oxide synthase (iNOS) expression in macrophage cell line, Raw 264.7 cells. When Raw 264.7 cells were stimulated with LPS, the expressions of PLDs were increased. Thus, to investigate the role of PLD in NO synthesis, we transfected PLD1, PLD2, and their dominant negative forms to Raw 264.7 cells, respectively. Interestingly, only PLD2 overexpression, but not that of PLD1, increased NO synthesis and iNOS expression. Moreover, LPS-induced NO synthesis and iNOS expression were blocked by PLD2 siRNA, suggesting that LPS upregulates NO synthesis through PLD2. Next, we investigated the S6K1-p42/44 MAPK-STAT3 signaling pathway in LPS-induced NO synthesis mechanism. Knockdown of PLD2 with siRNA also decreased phosphorylation of S6K1, p42/44 MAPK and STAT3 induced by LPS. Furthermore, we found that STAT3 bound with the iNOS promoter, and their binding was mediated by PLD2. Taken together, our results demonstrate the importance of PLD2 for LPS-induced NO synthesis in Raw 264.7 cells with involvement of the S6K1-p42/44 MAPK-STAT3 pathway. |
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