on May 29, 2003
Arteriosclerosis, Thrombosis, and Vascular Biology. 2003
Published online before print May 29, 2003, doi: 10.1161/01.ATV.0000079340.80744.B8
Published online before print May 29, 2003, doi: 10.1161/01.ATV.0000079340.80744.B8
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on March 17, 2003
Accepted on May 19, 2003
Specific Phospholipid Oxidation Products Inhibit Ligand Activation of Toll-Like Receptors 4 and 2
Kimberly A. Walton ;
From the Departments of Medicine (K.A.W., A.L.C., M.Y., G.S., R.M.L, J.N, D.K.V., J.A.B.), Pathology (K.A.W., M.Y., R.M.L, J.A.B.), and Microbiology and Immunology (S.R.K., R.L.M), University of California, Los Angeles; and the Department of Physiology (E.J.S.), University of Kentucky Medical School, Lexington.
* To whom correspondence should be addressed. E-mail: JBerliner{at}mednet.ucla.edu.
Objective--We have previously shown that phospholipid oxidation products of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (ox-PAPC) inhibit lipopolysaccharide (LPS)-induced E-selectin expression and neutrophil binding in human aortic endothelial cells (HAECs). The current studies identify specific phospholipids that inhibit chemokine induction by Toll-like receptor-4 (TLR4) and -2 (TLR2) ligands in ECs and macrophages.
Methods and Results--Measurements of interleukin (IL)-8 and monocyte chemotactic protein-1 levels secreted from ox-PAPC- and LPS-cotreated ECs indicate that ox-PAPC inhibits activation of TLR4 by LPS. The effects of IL-1
and tumor necrosis factor-
, which utilize the same intracellular signaling molecules, were not inhibited. Cell fractionation and immunofluorescence analyses demonstrate that LPS induces membrane translocation of the LPS receptor complex to a lipid raft/caveolar fraction in ECs. Ox-PAPC inhibits this translocation and alters caveolin-1 distribution. Supporting an important role for caveolae in LPS action, overexpression of caveolin-1 enhanced LPS-induced IL-8 synthesis. Ox-PAPC also inhibits the effect of TLR2 and TLR4 ligands in human macrophages.
Conclusions--These studies report a novel mechanism that involves alterations to lipid raft/caveolar processing, by which specific phospholipid oxidation products inhibit activation by TLR4 and TLR2 ligands. These studies have broader implications for the role of ox-PAPC as a regulator of specific lipid raft/caveolar function.
Key words: endothelial cells • oxidized phospholipids • lipopolysaccharide • Toll-like receptors • inflammation
This article has been cited by other articles:
 |
|
 |
|
  L. K. Curtiss and P. S. Tobias Emerging role of Toll-like receptors in atherosclerosis J. Lipid Res., April 1, 2009; 50(Supplement): S340 - S345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Berliner, N. Leitinger, and S. Tsimikas The role of oxidized phospholipids in atherosclerosis J. Lipid Res., April 1, 2009; 50(Supplement): S207 - S212. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Fu, A. A. Birukova, J. Xing, S. Sammani, J. S. Murley, J. G. N. Garcia, D. J. Grdina, and K. G. Birukov Amifostine reduces lung vascular permeability via suppression of inflammatory signalling Eur. Respir. J., March 1, 2009; 33(3): 612 - 624. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Erridge Oxidized Phospholipid Inhibition of LPS-Signaling: A Good Side to the Bad Guys? Arterioscler Thromb Vasc Biol, March 1, 2009; 29(3): 337 - 338. [Full Text] [PDF]
|
|
|
|
|
|
E. von Schlieffen, O. V. Oskolkova, G. Schabbauer, F. Gruber, S. Bluml, M. Genest, A. Kadl, C. Marsik, S. Knapp, J. Chow, et al. Multi-Hit Inhibition of Circulating and Cell-Associated Components of the Toll-Like Receptor 4 Pathway by Oxidized Phospholipids Arterioscler Thromb Vasc Biol, March 1, 2009; 29(3): 356 - 362. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liu, W. Hao, A. Dawson, S. Liu, and K. Fassbender Expression of Amyotrophic Lateral Sclerosis-linked SOD1 Mutant Increases the Neurotoxic Potential of Microglia via TLR2 J. Biol. Chem., February 6, 2009; 284(6): 3691 - 3699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. C. Parker, E. C. Prestwich, J. R. Ward, E. Smythe, A. Berry, M. Triantafilou, K. Triantafilou, and I. Sabroe A Phosphatidylserine Species Inhibits a Range of TLR- but Not IL-1{beta}-Induced Inflammatory Responses by Disruption of Membrane Microdomains J. Immunol., October 15, 2008; 181(8): 5606 - 5617. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Erridge, S. Kennedy, C. M. Spickett, and D. J. Webb Oxidized Phospholipid Inhibition of Toll-like Receptor (TLR) Signaling Is Restricted to TLR2 and TLR4: ROLES FOR CD14, LPS-BINDING PROTEIN, AND MD2 AS TARGETS FOR SPECIFICITY OF INHIBITION J. Biol. Chem., September 5, 2008; 283(36): 24748 - 24759. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. I. Duenas, M. Aceves, I. Fernandez-Pisonero, C. Gomez, A. Orduna, M. S. Crespo, and C. Garcia-Rodriguez Selective attenuation of Toll-like receptor 2 signalling may explain the atheroprotective effect of sphingosine 1-phosphate Cardiovasc Res, August 1, 2008; 79(3): 537 - 544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Davis, G. Koster, L. J. Douet, M. Scigelova, G. Woffendin, J. M. Ward, A. Smith, J. Humphries, K. G. Burnand, C. H. Macphee, et al. Electrospray Ionization Mass Spectrometry Identifies Substrates and Products of Lipoprotein-associated Phospholipase A2 in Oxidized Human Low Density Lipoprotein J. Biol. Chem., March 7, 2008; 283(10): 6428 - 6437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. M. Gharavi, J. A. Alva, K. P. Mouillesseaux, C. Lai, M. Yeh, W. Yeung, J. Johnson, W. L. Szeto, L. Hong, M. Fishbein, et al. 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., October 26, 2007; 282(43): 31460 - 31468. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Birukova, P. Fu, S. Chatchavalvanich, D. Burdette, O. Oskolkova, V. N. Bochkov, and K. G. Birukov Polar head groups are important for barrier-protective effects of oxidized phospholipids on pulmonary endothelium Am J Physiol Lung Cell Mol Physiol, April 1, 2007; 292(4): L924 - L935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Moumtzi, M. Trenker, K. Flicker, E. Zenzmaier, R. Saf, and A. Hermetter Import and fate of fluorescent analogs of oxidized phospholipids in vascular smooth muscle cells J. Lipid Res., March 1, 2007; 48(3): 565 - 582. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Heidemann, W. Domschke, T. Kucharzik, and C. Maaser Intestinal microvascular endothelium and innate immunity in inflammatory bowel disease: a second line of defense? Infect. Immun., October 1, 2006; 74(10): 5425 - 5432. [Full Text] [PDF]
|
|
|
|
|
|
K. A. Walton, B. G. Gugiu, M. Thomas, R. J. Basseri, D. R. Eliav, R. G. Salomon, and J. A. Berliner A role for neutral sphingomyelinase activation in the inhibition of LPS action by phospholipid oxidation products J. Lipid Res., September 1, 2006; 47(9): 1967 - 1974. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Nonas, I. Miller, K. Kawkitinarong, S. Chatchavalvanich, I. Gorshkova, V. N. Bochkov, N. Leitinger, V. Natarajan, J. G. N. Garcia, and K. G. Birukov Oxidized Phospholipids Reduce Vascular Leak and Inflammation in Rat Model of Acute Lung Injury Am. J. Respir. Crit. Care Med., May 15, 2006; 173(10): 1130 - 1138. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. M. Wang, H. P. Kim, R. Song, and A. M. K. Choi Caveolin-1 Confers Antiinflammatory Effects in Murine Macrophages via the MKK3/p38 MAPK Pathway Am. J. Respir. Cell Mol. Biol., April 1, 2006; 34(4): 434 - 442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Rumbaut, R. V. Bellera, J. K. Randhawa, C. N. Shrimpton, S. K. Dasgupta, J.-F. Dong, and A. R. Burns Endotoxin enhances microvascular thrombosis in mouse cremaster venules via a TLR4-dependent, neutrophil-independent mechanism Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1671 - H1679. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Mehta and A. B. Malik Signaling Mechanisms Regulating Endothelial Permeability Physiol Rev, January 1, 2006; 86(1): 279 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bluml, S. Kirchberger, V. N. Bochkov, G. Kronke, K. Stuhlmeier, O. Majdic, G. J. Zlabinger, W. Knapp, B. R. Binder, J. Stockl, et al. Oxidized Phospholipids Negatively Regulate Dendritic Cell Maturation Induced by TLRs and CD40 J. Immunol., July 1, 2005; 175(1): 501 - 508. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. K. Hansson and K. Edfeldt Toll To Be Paid at the Gateway to the Vessel Wall Arterioscler Thromb Vasc Biol, June 1, 2005; 25(6): 1085 - 1087. [Full Text] [PDF]
|
|
|
|
|
|
Y. I. Miller, S. Viriyakosol, D. S. Worrall, A. Boullier, S. Butler, and J. L. Witztum Toll-Like Receptor 4-Dependent and -Independent Cytokine Secretion Induced by Minimally Oxidized Low-Density Lipoprotein in Macrophages Arterioscler Thromb Vasc Biol, June 1, 2005; 25(6): 1213 - 1219. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. S. Goodridge, F. A. Marshall, K. J. Else, K. M. Houston, C. Egan, L. Al-Riyami, F.-Y. Liew, W. Harnett, and M. M. Harnett Immunomodulation via Novel Use of TLR4 by the Filarial Nematode Phosphorylcholine-Containing Secreted Product, ES-62 J. Immunol., January 1, 2005; 174(1): 284 - 293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Nilsson, G. K. Hansson, and P. K. Shah Immunomodulation of Atherosclerosis: Implications for Vaccine Development Arterioscler Thromb Vasc Biol, January 1, 2005; 25(1): 18 - 28. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. S. Michelsen, T. M. Doherty, P. K. Shah, and M. Arditi Role of Toll-Like Receptors in Atherosclerosis Circ. Res., December 10, 2004; 95(12): e96 - e97. [Full Text] [PDF]
|
|
|
|
|
|
K. S. Michelsen, T. M. Doherty, P. K. Shah, and M. Arditi TLR Signaling: An Emerging Bridge from Innate Immunity to Atherogenesis J. Immunol., November 15, 2004; 173(10): 5901 - 5907. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yeh, A. L. Cole, J. Choi, Y. Liu, D. Tulchinsky, J.-H. Qiao, M. C. Fishbein, A. N. Dooley, T. Hovnanian, K. Mouilleseaux, et al. Role for Sterol Regulatory Element-Binding Protein in Activation of Endothelial Cells by Phospholipid Oxidation Products Circ. Res., October 15, 2004; 95(8): 780 - 788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Mullaly and P. Kubes Toll Gates and Traffic Arteries: From Endothelial TLR2 to Atherosclerosis Circ. Res., October 1, 2004; 95(7): 657 - 659. [Full Text] [PDF]
|
|
|
|
|
|
M. Yeh, N. M. Gharavi, J. Choi, X. Hsieh, E. Reed, K. P. Mouillesseaux, A. L. Cole, S. T. Reddy, and J. A. Berliner 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., July 16, 2004; 279(29): 30175 - 30181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Marson, R. M. Lawn, and T. Mikita Oxidized Low Density Lipoprotein Blocks Lipopolysaccharide-induced Interferon {beta} Synthesis in Human Macrophages by Interfering with IRF3 Activation J. Biol. Chem., July 2, 2004; 279(27): 28781 - 28788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Khovidhunkit, M.-S. Kim, R. A. Memon, J. K. Shigenaga, A. H. Moser, K. R. Feingold, and C. Grunfeld Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host J. Lipid Res., July 1, 2004; 45(7): 1169 - 1196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Y. Lee, L. Zhao, H. S. Youn, A. R. Weatherill, R. Tapping, L. Feng, W. H. Lee, K. A. Fitzgerald, and D. H. Hwang Saturated Fatty Acid Activates but Polyunsaturated Fatty Acid Inhibits Toll-like Receptor 2 Dimerized with Toll-like Receptor 6 or 1 J. Biol. Chem., April 23, 2004; 279(17): 16971 - 16979. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Mackman How Do Oxidized Phospholipids Inhibit LPS Signaling? Arterioscler Thromb Vasc Biol, July 1, 2003; 23(7): 1133 - 1136. [Full Text] [PDF]
|
|