© 2000 American Heart Association, Inc.
Integrative Physiology |
Requisite Role for Interleukin-4 in the Acceleration of Fatty Streaks Induced by Heat Shock Protein 65 or Mycobacterium tuberculosis
From the Research Unit of Autoimmune Diseases (J.G., Y.S., B.G.); Department of Medicine "B," Institute of Pathology (A.A.); and Institute of Lipid and Atherosclerosis Research (A.S., D.H.), Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Correspondence and reprint requests to Dror Harats, MD, Institute of Lipid and Atherosclerosis Research, Sheba Medical Center, Tel-Hashomer, 52621, Israel. E-mail dharats{at}post.tau.ac.il
Abstract—Atherosclerotic lesions
can be induced in rabbits and mice immunized with heat shock protein 65
(HSP65). In the current study, we investigated the role of interleukin
(IL)-4 in the HSP65- and Mycobacterium tuberculosis
(MT)–induced models that exhibit an inflammatory phenotype.
Fatty streak formation in IL-4–knockout (IL-4 KO) mice immunized with
HSP65 or MT was significantly reduced when compared with lesions in
wild-type C57BL/6 mice. However, when injected with control (HSP-free)
adjuvant, no differences were evident in the lesion size between
wild-type and the IL-4 KO mice. Next, we studied comparatively the
extent of humoral and cellular immune responses to HSP65 in the IL-4 KO
and wild-type mice, as those are thought to be influential in murine
atherosclerosis. Anti-HSP65 antibody levels were
reduced in the HSP65-immunized IL-4 KO mice as compared with their
wild-type littermates, whereas no differences were evident between the
groups with respect to the primary cellular immune response to HSP65.
Other than the absence of IL-4 in the knockout mice, the pattern of
secreting cytokines interferon-
and IL-10 in concanavalin
A–primed splenocytes was similar between the groups.
HSP65-primed inguinal lymphocytes from IL-4 KO mice immunized with
HSP65 secreted higher levels of interferon- (previously shown to be
proatherogenic in vivo) as compared with their wild-type controls.
12-/15-Lipoxygenase expression, known to be regulated
by IL-4 and to contribute to murine atherosclerosis, in
the lesions was not influenced by the immunization protocol used or by
IL-4 disruption. Thus, IL-4 may prove a principal cytokine in
the progression of early "inflammatory" atherosclerotic lesions and
may serve as a target for immunomodulation.
Key Words: atherosclerosis • autoantibodies • heat shock proteins • interleukins • Mycobacterium tuberculosis
This article has been cited by other articles:
 |
|
 |
|
  R. Kleemann, S. Zadelaar, and T. Kooistra Cytokines and atherosclerosis: a comprehensive review of studies in mice Cardiovasc Res, August 1, 2008; 79(3): 360 - 376. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. L. King, L. A. Cassis, and A. Daugherty Interleukin-4 Does Not Influence Development of Hypercholesterolemia or Angiotensin II-Induced Atherosclerotic Lesions in Mice Am. J. Pathol., December 1, 2007; 171(6): 2040 - 2047. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Tedgui and Z. Mallat Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways Physiol Rev, April 1, 2006; 86(2): 515 - 581. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Lepper, W. Koenig, P. Moller, and S. Perner A Case of Sudden Cardiac Death Due to Isolated Eosinophilic Coronary Arteritis Chest, August 1, 2005; 128(2): 1047 - 1050. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. George, N. Yacov, E. Breitbart, L. Bangio, A. Shaish, B. Gilburd, Y. Shoenfeld, and D. Harats Suppression of early atherosclerosis in LDL-receptor deficient mice by oral tolerance with {beta}2-glycoprotein I Cardiovasc Res, June 1, 2004; 62(3): 603 - 609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Davenport and P. G. Tipping The Role of Interleukin-4 and Interleukin-12 in the Progression of Atherosclerosis in Apolipoprotein E-Deficient Mice Am. J. Pathol., September 1, 2003; 163(3): 1117 - 1125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Von der Thusen, J. Kuiper, T. J. C. Van Berkel, and E. A. L. Biessen Interleukins in Atherosclerosis: Molecular Pathways and Therapeutic Potential Pharmacol. Rev., March 1, 2003; 55(1): 133 - 166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Harats, N. Yacov, B. Gilburd, Y. Shoenfeld, and J. George Oral tolerance with heat shock protein 65 attenuates mycobacterium tuberculosis-inducedand high-fat-diet-driven atherosclerotic lesions J. Am. Coll. Cardiol., October 2, 2002; 40(7): 1333 - 1338. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Schonbeck, G. K. Sukhova, N. Gerdes, and P. Libby TH2 Predominant Immune Responses Prevail in Human Abdominal Aortic Aneurysm Am. J. Pathol., August 1, 2002; 161(2): 499 - 506. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. George, A. Afek, P. Keren, I. Herz, I. Goldberg, R. Haklai, Y. Kloog, and G. Keren Functional Inhibition of Ras by S-trans,trans-Farnesyl Thiosalicylic Acid Attenuates Atherosclerosis in Apolipoprotein E Knockout Mice Circulation, May 21, 2002; 105(20): 2416 - 2422. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y Sherer and Y Shoenfeld Atherosclerosis Ann Rheum Dis, February 1, 2002; 61(2): 97 - 99. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. George, A. Afek, A. Shaish, H. Levkovitz, N. Bloom, T. Cyrus, L. Zhao, C. D. Funk, E. Sigal, and D. Harats 12/15-Lipoxygenase Gene Disruption Attenuates Atherogenesis in LDL Receptor-Deficient Mice Circulation, October 2, 2001; 104(14): 1646 - 1650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. George, A. Afek, B. Gilburd, Y. Shoenfeld, and D. Harats Cellular and humoral immune responses to heat shock protein 65 are both involved in promoting fatty-streak formation in LDL-receptor deficient mice J. Am. Coll. Cardiol., September 1, 2001; 38(3): 900 - 905. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Tedgui and Z. Mallat Anti-Inflammatory Mechanisms in the Vascular Wall Circ. Res., May 11, 2001; 88(9): 877 - 887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhu, A. A. Quyyumi, D. Rott, G. Csako, H. Wu, J. Halcox, and S. E. Epstein Antibodies to Human Heat-Shock Protein 60 Are Associated With the Presence and Severity of Coronary Artery Disease : Evidence for an Autoimmune Component of Atherogenesis Circulation, February 27, 2001; 103(8): 1071 - 1075. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Mallat, A. Gojova, C. Marchiol-Fournigault, B. Esposito, C. Kamate, R. Merval, D. Fradelizi, and A. Tedgui Inhibition of Transforming Growth Factor-{beta} Signaling Accelerates Atherosclerosis and Induces an Unstable Plaque Phenotype in Mice Circ. Res., November 9, 2001; 89(10): 930 - 934. [Abstract] [Full Text] [PDF]
|
|