Oral tolerization with cardiac myosin peptide (614-629) ameliorates experimental autoimmune myocarditis: role of STAT 6 genes in BALB/CJ mice.

Abstract

INTRODUCTION:

Experimental autoimmune myocarditis (EAM) is mediated by myocardial infiltration by myosin-specific T cells secreting inflammatory cytokines.

MATERIALS AND METHODS:

To clarify the role of cytokines in EAM, we compared STAT 6-deficient ((-/-)) with STAT 4(-/-) and wild-type (BALB/CJ) mice following immunization with cardiac myosin peptide (614-629).

RESULTS:

Wild-type mice developed severe disease with a small increase in severity in STAT 6(-/-) mice, while STAT 4(-/-) mice were resistant to EAM. STAT 6(-/-) mice had increased splenocyte proliferation and INF-gamma production versus wild type, while STAT 4(-/-) mice had decreased proliferation and INF-gamma. Following oral administration of myosin (614-629), tolerization was induced in wild-type mice evidenced by amelioration of myocarditis and up-regulation of IL-4. Adoptive transfer of splenocytes from orally tolerized mice resulted in inhibition of disease in STAT 6(-/-) mice.

CONCLUSION:

These results demonstrate that oral tolerization ameliorates EAM in BALB/CJ mice and indicate a down-regulatory role for STAT 6 genes.

• Authors: Patricia A Gonnella, Pedro J Del Nido, Francis X McGowan
• Journal: Journal of clinical immunology (J Clin Immunol) Vol. 29 Issue 4 Pg. 434-43 (Jul 2009) ISSN: 1573-2592 [Electronic] Netherlands
• PMID: 19353248 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Peptides
• STAT4 Transcription Factor
• STAT6 Transcription Factor
• Stat4 protein, mouse
• Stat6 protein, mouse
• Interleukin-4
• Interferon-gamma
• Cardiac Myosins

Topics

• Administration, Oral
• Adoptive Transfer
• Animals
• Autoimmune Diseases (immunology, pathology)
• Cardiac Myosins (administration & dosage, immunology)
• Immune Tolerance
• Interferon-gamma (biosynthesis, immunology)
• Interleukin-4 (biosynthesis, immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Myocarditis (immunology, pathology)
• Peptides (administration & dosage, immunology)
• STAT4 Transcription Factor (genetics, immunology, metabolism)
• STAT6 Transcription Factor (genetics, immunology, metabolism)
• Spleen (immunology, metabolism)