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Requisite Role for Interleukin-4 in the Acceleration of Fatty Streaks Induced by Heat Shock Protein 65 or Mycobacterium tuberculosis
- Source :
- Circulation Research. 86:1203-1210
- Publication Year :
- 2000
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2000.
-
Abstract
- 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-γ 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-γ (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.
- Subjects :
- Cellular immunity
Chaperonins
Arteriosclerosis
Physiology
Ratón
Arachidonate 12-Lipoxygenase
Antibodies
Mycobacterium tuberculosis
Pathogenesis
Interferon-gamma
Mice
Immune system
Bacterial Proteins
Reference Values
Heat shock protein
Animals
Arachidonate 15-Lipoxygenase
Lymphocytes
Interleukin 4
Mice, Knockout
biology
Interleukin
Chaperonin 60
biology.organism_classification
Molecular biology
Interleukin-10
Mice, Inbred C57BL
Cholesterol
Immunology
Macrophages, Peritoneal
Female
Immunization
Interleukin-4
Cardiology and Cardiovascular Medicine
Cell Division
Subjects
Details
- ISSN :
- 15244571 and 00097330
- Volume :
- 86
- Database :
- OpenAIRE
- Journal :
- Circulation Research
- Accession number :
- edsair.doi.dedup.....401ab45e2eda182cf0302f82dd45a2e6