Microarray analysis reveals the role of matrix metalloproteinases in mouse experimental autoimmune myocarditis induced by cardiac myosin peptides.
Autoimmune myocarditis develops after the presentation of heart-specific antigens to autoaggressive CD4(+) T cells and after inflammation has infiltrated the tissues. To shed light on global changes in the gene expression of autoimmune myocarditis and to gain further insight into the molecular mechanisms underlying the genesis of myocarditis, we conducted a comprehensive microarray analysis of mRNA using an experimental mouse autoimmune myocarditis model via immunization with alpha-myosin heavy chain-derived peptides. Of over 39,000 transcripts on a high density oligonucleotide microarray, 466 were under-expressed and 241 over-expressed by >or= 1.5-fold compared with the controls in BALB/C mouse with autoimmune myocarditis. In this paper, we list the top 50 up-regulated genes related to the immune response. These altered genes encode for leukocyte-specific markers and receptors, the histocompatibility complex, cytokines/receptors, chemokines/receptors, adhesion molecules, components of the complement cascade, and signal transduction-related molecules. Interestingly, matrix metalloproteinases (MMPs) such as MMP-3 and MMP-9 were up-regulated, as further revealed by the reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry assays. This indicates that MMPs may act as major regulators of the cytokine profile. Together, these findings provide new insight into the molecular events associated with the mechanism of the autoimmune genesis of myocarditis.
Tang
Qizhu
Q
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China. qzhtang@yahoo.com
Huang
Ji
J
Qian
Haiyan
H
Xiong
Ran
R
Shen
Difei
D
Wu
Hui
H
Bian
Zhouyan
Z
Wei
Xiaohong
X
D000818:Animals; D024722:Cardiac Myosins / Q000494:pharmacology*; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D046228:Microarray Analysis; D009205:Myocarditis / Q000139:chemically induced* / Q000201:enzymology* / Q000235:genetics; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D009929:Organ Size; D010455:Peptides / Q000494:pharmacology*; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
D053583:Interleukin-1beta; D010455:Peptides; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D024722:Cardiac Myosins