Hypomethylation of perforin regulatory elements in CD4+ T cells from rat spleens contributes to the development of autoimmune emphysema.

Abstract

BACKGROUND AND OBJECTIVE:

It is widely accepted that perforin regulatory elements are hypomethylated in CD4+ T cells from patients with active lupus, but whether this is the case in autoimmune emphysema is not known.

METHODS:

Twenty rats were randomly divided into a normal control group and an emphysema group. Rat models of emphysema were established by intraperitoneal injection with xenogeneic endothelial cells. The levels of tumour necrosis factor-α, interleukin-8 and matrix metalloproteinase (MMP)-9 in bronchoalveolar lavage fluid (BALF) were measured, lung mean linear intercept and destructive index measured. Mean methylation of perforin gene promoter in CD4+ T cells and the expression of perforin were investigated. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling methods were used to examine the percentage of apoptotic cells in the alveolar septa.

RESULTS:

The levels of MMP-9 in BALF were higher in emphysema group than in control group (P < 0.05). The mean linear intercept and destructive index were higher in emphysema group than in control group (P < 0.05). The mean perforin gene promotor methylation of emphysema group was significantly decreased as compared with control group, while the expression levels of perforin gene were relatively higher (P < 0.05). There were more terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling-positive cells in the alveolar septa in control group than in emphysema group.

CONCLUSIONS:

Hypomethylation of perforin regulatory elements in CD4+ T cells may result in the lung septal cell apoptosis associated with the development of experimental autoimmune emphysema. MMP-9 may play an important role in the pathogenesis of this kind of disease.

• Authors: Cheng Zhang, Mu-Yun Yan, Ping Lu, Ping Chen, Min Yang, Xian-Wei Ye, Mei Xu, Zhang-Hong Ou Yang, Xiang-Yan Zhang
• Journal: Respirology (Carlton, Vic.) (Respirology) Vol. 19 Issue 3 Pg. 376-81 (Apr 2014) ISSN: 1440-1843 [Electronic] Australia
• PMID: 24506670 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 The Authors. Respirology © 2014 Asian Pacific Society of Respirology.

Chemical References

• Interleukin-8
• Pore Forming Cytotoxic Proteins
• Tumor Necrosis Factor-alpha
• perforin, rat
• Matrix Metalloproteinase 9

Topics

• Animals
• Autoimmune Diseases (genetics, metabolism)
• Bronchoalveolar Lavage Fluid
• CD4-Positive T-Lymphocytes (metabolism)
• Cell Culture Techniques
• DNA Methylation
• Disease Models, Animal
• In Situ Nick-End Labeling
• Interleukin-8 (metabolism)
• Male
• Matrix Metalloproteinase 9 (metabolism)
• Pore Forming Cytotoxic Proteins (genetics, metabolism)
• Pulmonary Emphysema (genetics, metabolism, pathology)
• Rats
• Rats, Sprague-Dawley
• Real-Time Polymerase Chain Reaction
• Regulatory Elements, Transcriptional (genetics)
• Sequence Analysis, DNA
• Spleen (cytology, metabolism)
• Tumor Necrosis Factor-alpha (metabolism)