Regulation of Monocyte Endothelial Interactions My research deals with the events mediating chronic inflammatory processes such as occur in atherosclerosis, cancer and rheumatoid arhtritis. Our research employs cell, molecular and biochemical methods to address several questions related to the regulation of the specific interaction of endothelial cells with monocytes. We have shown by Mass Spectroscopy and HPLC that particular oxidized phospholipids play a major role in activating endothelial cells to increase their interaction with monocytes. We have demonstrated that these phospholipid oxidation products are increased in cells exposed to oxidative stress, viral infection and are increased in atherosclerotic lesions. Current studies are focused on identifying the novel receptors for these lipids and the transcriptional and signal transduction pathways activated by them. For these studies we are employing a number of basic molecular biology methods as well as microarrays, proteomics and RNAi. Several candidate receptors and pathways have now been identified using cell culture. To verify their role, in vivo, human disease tissue is being analyzed for activation of particular pathways. In addition, we are testing the role of candidates by over and underexpression in mice using endothelial specific promoters. These studies should allow identification of important and novel pathways mediating chronic inflammatory diseases.
Gharavi, N. M. Alva, J. A. Mouillesseaux, K. P. Lai, C. Yeh, M. Yeung, W. Johnson, J. Szeto, W. L. Hong, L. Fishbein, M. Wei, L. Pfeffer, L. M. Berliner, J. A. Role of the Jak/STAT pathway in the regulation of interleukin-8 transcription by oxidized phospholipids in vitro and in atherosclerosis in vivo J Biol Chem, 2007; 282(43): 31460-8.
Gharavi, N. M. Gargalovic, P. S. Chang, I. Araujo, J. A. Clark, M. J. Szeto, W. L. Watson, A. D. Lusis, A. J. Berliner, J. A. High-density lipoprotein modulates oxidized phospholipid signaling in human endothelial cells from proinflammatory to anti-inflammatory Arterioscler Thromb Vasc Biol, 2007; 27(6): 1346-53.
Li, R. Chen, W. Yanes, R. Lee, S. Berliner, J. A. OKL38 is an oxidative stress response gene stimulated by oxidized phospholipids J Lipid Res, 2007; 48(3): 709-15.
Zimman, A. Mouillesseaux, K. P. Le, T. Gharavi, N. M. Ryvkin, A. Graeber, T. G. Chen, T. T. Watson, A. D. Berliner, J. A. Vascular endothelial growth factor receptor 2 plays a role in the activation of aortic endothelial cells by oxidized phospholipids Arterioscler Thromb Vasc Biol, 2007; 27(2): 332-8.
Gargalovic, P. S. Imura, M. Zhang, B. Gharavi, N. M. Clark, M. J. Pagnon, J. Yang, W. P. He, A. Truong, A. Patel, S. Nelson, S. F. Horvath, S. Berliner, J. A. Kirchgessner, T. G. Lusis, A. J. Identification of inflammatory gene modules based on variations of human endothelial cell responses to oxidized lipids Proc Natl Acad Sci U S A, 2006; 103(34): 12741-6.
Walton, K. A. Gugiu, B. G. Thomas, M. Basseri, R. J. Eliav, D. R. Salomon, R. G. Berliner, J. A. A role for neutral sphingomyelinase activation in the inhibition of LPS action by phospholipid oxidation products J Lipid Res, 2006; 47(9): 1967-74.
Gargalovic, P. S. Gharavi, N. M. Clark, M. J. Pagnon, J. Yang, W. P. He, A. Truong, A. Baruch-Oren, T. Berliner, J. A. Kirchgessner, T. G. Lusis, A. J. The unfolded protein response is an important regulator of inflammatory genes in endothelial cells Arterioscler Thromb Vasc Biol, 2006; 26(11): 2490-6.
Gharavi, N. M. Baker, N. A. Mouillesseaux, K. P. Yeung, W. Honda, H. M. Hsieh, X. Yeh, M. Smart, E. J. Berliner, J. A. Role of endothelial nitric oxide synthase in the regulation of SREBP activation by oxidized phospholipids Circ Res, 2006; 98(6): 768-76.
Li, R. Mouillesseaux, K. P. Montoya, D. Cruz, D. Gharavi, N. Dun, M. Koroniak, L. Berliner, J. A. Identification of prostaglandin E2 receptor subtype 2 as a receptor activated by OxPAPC Circ Res, 2006; 98(5): 642-50.
Chang, M. K. Binder, C. J. Miller, Y. I. Subbanagounder, G. Silverman, G. J. Berliner, J. A. Witztum, J. L. Apoptotic cells with oxidation-specific epitopes are immunogenic and proinflammatory J Exp Med, 2004; 200(11): 1359-70.
Yeh, M. Cole, A. L. Choi, J. Liu, Y. Tulchinsky, D. Qiao, J. H. Fishbein, M. C. Dooley, A. N. Hovnanian, T. Mouilleseaux, K. Vora, D. K. Yang, W. P. Gargalovic, P. Kirchgessner, T. Shyy, J. Y. Berliner, J. A. Role for sterol regulatory element-binding protein in activation of endothelial cells by phospholipid oxidation products Circ Res, 2004; 95(8): 780-8.
Yeh, M Cole, AL Choi, J Liu, Y Tulchinsky, D Qiao, JH Fishbein, MC Dooley, AN Hovnanian, T Mouilleseaux, K Vora, DK Yang, WP Gargalovic, P Kirchgessner, T Shyy, JY Berliner, JA Role for sterol regulatory element-binding protein in activation of endothelial cells by phospholipid oxidation products Circulation research. , 2004; 95(8): 780-8.
Yeh, M. Gharavi, N. M. Choi, J. Hsieh, X. Reed, E. Mouillesseaux, K. P. Cole, A. L. Reddy, S. T. Berliner, J. A. Oxidized phospholipids increase interleukin 8 (IL-8) synthesis by activation of the c-src/signal transducers and activators of transcription (STAT)3 pathway J Biol Chem, 2004; 279(29): 30175-81.
Chatterjee, S. Berliner, J. A. Subbanagounder, G. G. Bhunia, A. K. Koh, S. Identification of a biologically active component in minimally oxidized low density lipoprotein (MM-LDL) responsible for aortic smooth muscle cell proliferation Glycoconj J, 2004; 20(5): 331-8.
Kim, J. A. Tran, N. D. Berliner, J. A. Fisher, M. J. Minimally oxidized low-density lipoprotein regulates hemostasis factors of brain capillary endothelial cells J Neurol Sci, 2004; 217(2): 135-41.
Walton, K. A. Hsieh, X. Gharavi, N. Wang, S. Wang, G. Yeh, M. Cole, A. L. Berliner, J. A. Receptors involved in the oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine-mediated synthesis of interleukin-8. A role for Toll-like receptor 4 and a glycosylphosphatidylinositol-anchored protein J Biol Chem, 2003; 278(32): 29661-6.
Cole, A. L. Subbanagounder, G. Mukhopadhyay, S. Berliner, J. A. Vora, D. K. Oxidized phospholipid-induced endothelial cell/monocyte interaction is mediated by a cAMP-dependent R-Ras/PI3-kinase pathway Arterioscler Thromb Vasc Biol, 2003; 23(8): 1384-90.
Walton, K. A. Cole, A. L. Yeh, M. Subbanagounder, G. Krutzik, S. R. Modlin, R. L. Lucas, R. M. Nakai, J. Smart, E. J. Vora, D. K. Berliner, J. A. Specific phospholipid oxidation products inhibit ligand activation of toll-like receptors 4 and 2 Arterioscler Thromb Vasc Biol, 2003; 23(7): 1197-203.
Srinivasan, S. Yeh, M. Danziger, E. C. Hatley, M. E. Riggan, A. E. Leitinger, N. Berliner, J. A. Hedrick, C. C. Glucose regulates monocyte adhesion through endothelial production of interleukin-8 Circ Res, 2003; 92(4): 371-7.
Jung, M. E. Kers, A. Subbanagounder, G. Berliner, J. A. Studies towards the total synthesis of an epoxy isoprostane phospholipid, a potent activator of endothelial cells Chem Commun (Camb), 2003; (2): 196-7.
Subbanagounder, G Wong, JW Lee, H Faull, KF Miller, E Witztum, JL Berliner, JA Epoxyisoprostane and epoxycyclopentenone phospholipids regulate monocyte chemotactic protein-1 and interleukin-8 synthesis. Formation of these oxidized phospholipids in response to interleukin-1beta The Journal of biological chemistry. , 2002; 277(9): 7271-81.
Yeh, M Leitinger, N de Martin, R Onai, N Matsushima, K Vora, DK Berliner, JA Reddy, ST Increased transcription of IL-8 in endothelial cells is differentially regulated by TNF-alpha and oxidized phospholipids Arteriosclerosis, thrombosis, and vascular biology. , 2001; 21(10): 1585-91.
Subbanagounder, G Leitinger, N Schwenke, DC Wong, JW Lee, H Rizza, C Watson, AD Faull, KF Fogelman, AM Berliner, JA Determinants of bioactivity of oxidized phospholipids. Specific oxidized fatty acyl groups at the sn-2 position Arteriosclerosis, thrombosis, and vascular biology. , 2000; 20(10): 2248-54.
Lee, H Shi, W Tontonoz, P Wang, S Subbanagounder, G Hedrick, CC Hama, S Borromeo, C Evans, RM Berliner, JA Nagy, L Role for peroxisome proliferator-activated receptor alpha in oxidized phospholipid-induced synthesis of monocyte chemotactic protein-1 and interleukin-8 by endothelial cells Circulation research. , 2000; 87(6): 516-21.
Pinderski Oslund, LJ Hedrick, CC Olvera, T Hagenbaugh, A Territo, M Berliner, JA Fyfe, AI Interleukin-10 blocks atherosclerotic events in vitro and in vivo Arteriosclerosis, thrombosis, and vascular biology. , 1999; 19(12): 2847-53.
Leitinger, N Tyner, TR Oslund, L Rizza, C Subbanagounder, G Lee, H Shih, PT Mackman, N Tigyi, G Territo, MC Berliner, JA Vora, DK Structurally similar oxidized phospholipids differentially regulate endothelial binding of monocytes and neutrophils Proceedings of the National Academy of Sciences of the United States of America. , 1999; 96(21): 12010-5.
Watson, AD Subbanagounder, G Welsbie, DS Faull, KF Navab, M Jung, ME Fogelman, AM Berliner, JA Structural identification of a novel pro-inflammatory epoxyisoprostane phospholipid in mildly oxidized low density lipoprotein The Journal of biological chemistry. , 1999; 274(35): 24787-98.
Subbanagounder G, Leitinger N, Shih PT, Faull KF, Lee H and Berliner JA. Evidence that phospholipid oxidation products and/or platelet activating factor play an important role in early atherogenesis: In vitro and in vivo inhibition by WEB 2086, Circ Res, 1999; 85: 311-318.
Honda HM, Leitinger N, Frankel M, Goldhaber JI, Natarajan R, Weiss JN, Nadler J and Berliner JA. Induction of monocyte binding to endothelial cells by MM-LDL: the role of lipoxygenase metabolies, Arterio Throm and Vasc Biol, 1999; 19: 680-686.
Rizza C, Leitinger N, Junming Y, Fischer DJ, Wang D, Shih PT, Lee H, Tigyi G and Berliner JA Lysophosphatidic acid as a regulator of endothelial/leukocyte interaction, Lab Invest, 1999; 79: 1227-1235.
Shih PT, Elices MJ, Fang ZT, Ugarova TP, Strahl D, Territo MC, Frank JS, Kovach NL, Cabanas C, Berliner JA and Vora DK. MM-LDL induces monocyte adhesion to endothelial CS-1 by activating Beta 1 integrin, J Clin Invest, 1999; 103: 613-625.
Leitinger N, Watson AD, Hama SY, Ivandic B, Qiao J, Huber J, Faull KF, Grass DS, Navab M, Fogelman AM, DeBeer F, Lusis A and Berliner JA. Rose of Group II secretory PLA2 in atherosclerosis, Arterio Throm and Vasc Biol, 1999; 19: 1291-1298.
Honda, HM Leitinger, N Frankel, M Goldhaber, JI Natarajan, R Nadler, JL Weiss, JN Berliner, JA Induction of monocyte binding to endothelial cells by MM-LDL: role of lipoxygenase metabolites Arteriosclerosis, thrombosis, and vascular biology. , 1999; 19(3): 680-6.
Shih, PT Brennan, ML Vora, DK Territo, MC Strahl, D Elices, MJ Lusis, AJ Berliner, JA Blocking very late antigen-4 integrin decreases leukocyte entry and fatty streak formation in mice fed an atherogenic diet Circulation research. , 1999; 84(3): 345-51.
Watson AD, Leitinger N ....and Berliner JA Identification by Mass Spectrometry of Oxidized phospholipids in minimally oxidized LDL that induce monoocyte/endothelial intereactions and evidence for their presence in vivo, J Biol Chem, 1997; 272: 13597-13607.
Watson AD, Leitinger N, Navab M, Faull KF, Horkko S, Witztum JL, Palinski W, Schwenke D, Salomon RG, Sha W, Subbanagounder G, Fogelman AM and Berliner JA. Structual Identification by mass spectrometry of oxidized phospholipids in minimally oxidized LDL that induce monocyte/endothelial interactions and evidence for their presence in vivo, J. Biol Chem, 1997; 272: 13597-13607.
Vora, DK Fang, ZT Liva, SM Tyner, TR Parhami, F Watson, AD Drake, TA Territo, MC Berliner, JA Induction of P-selectin by oxidized lipoproteins. Separate effects on synthesis and surface expression Circulation research. , 1997; 80(6): 810-8.
Watson, AD Berliner, JA Hama, SY La Du, BN Faull, KF Fogelman, AM Navab, M Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein The Journal of clinical investigation. , 1995; 96(6): 2882-91.
Parhami, F Fang, ZT Yang, B Fogelman, AM Berliner, JA Stimulation of Gs and inhibition of Gi protein functions by minimally oxidized LDL Arteriosclerosis, thrombosis, and vascular biology. , 1995; 15(11): 2019-24.
Berliner, JA Territo, MC Sevanian, A Ramin, S Kim, JA Bamshad, B Esterson, M Fogelman, AM Minimally modified low density lipoprotein stimulates monocyte endothelial interactions The Journal of clinical investigation. , 1990; 85(4): 1260-6.
Does this profile need updating? Contact Us