Oral tolerance with heat shock protein 65 attenuates Mycobacterium tuberculosis-induced and high-fat-diet-driven atherosclerotic lesions.

Abstract

OBJECTIVE:

The goal of this study was to explore the efficacy of oral tolerance with heat shock protein (HSP) 65 in two apparently non-overlapping models of murine atherosclerosis.

BACKGROUND:

Atherosclerosis is considered to be a chronic inflammatory process. Autoimmune mechanisms have been shown to influence atherogenesis in experimental animal models. Heat shock protein 65 is a candidate antigen thought to drive a proatherogenic immune-mediated response. Mucosal tolerance is a therapeutic means of accomplishing immune unresponsiveness toward a given antigen by feeding it before active induction of the disorder.

METHODS:

Low-density lipoprotein receptor deficient mice were fed with different doses of HSP65 every other day for 10 days. Feeding with either bovine serum albumin (BSA) or phosphate buffered saline (PBS) served as control. One day after the last feeding, mice were challenged either by immunization with heat killed Mycobacterium tuberculosis or by a high fat diet.

RESULTS:

Lymphocyte reactivity from mice fed with HSP65 and immunized either against HSP65 or M. tuberculosis was significantly reduced in comparison with BSA-fed mice. Moreover, co-incubation of splenocytes-from mice with tolerance induced with HSP65 but not BSA-with HSP65-reactive lymphocytes resulted in the suppression of HSP65 reactivity by the latter cells. Interleukin-4 production by HSP65-fed and immunized mice was increased upon priming with respective protein. Early atherosclerosis was attenuated in HSP65-fed mice, compared with either BSA- or PBS-fed mice, regardless of the method employed to induce fatty streaks (M. tuberculosis immunization or high-fat diet).

CONCLUSIONS:

Oral tolerance induced with HSP65 could prove to be a novel means of suppressing atherogenesis.

• Authors: Dror Harats, Niva Yacov, Boris Gilburd, Yehuda Shoenfeld, Jacob George
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 40 Issue 7 Pg. 1333-8 (Oct 02 2002) ISSN: 0735-1097 [Print] United States
• PMID: 12383583 (Publication Type: Journal Article)

Chemical References

• Bacterial Proteins
• Chaperonin 60
• Receptors, LDL
• heat-shock protein 65, Mycobacterium
• Chaperonins

Topics

• Administration, Oral
• Analysis of Variance
• Animals
• Arteriosclerosis (etiology, immunology, pathology, prevention & control)
• Autoimmune Diseases (etiology, immunology, pathology, prevention & control)
• Bacterial Proteins
• Chaperonin 60
• Chaperonins (immunology, therapeutic use)
• Clonal Anergy (immunology)
• Diet, Atherogenic
• Disease Models, Animal
• Female
• Immune Tolerance
• Immunity, Mucosal
• Immunohistochemistry
• Mice
• Mice, Inbred Strains
• Mycobacterium tuberculosis (immunology)
• Receptors, LDL (deficiency)
• Th2 Cells (immunology)