Expression of B7-1, B7-2, and interleukin-12 in anti-Fas antibody-induced pulmonary fibrosis in mice.
BACKGROUND
We have previously reported that the inhalation of anti-Fas antibody induced pulmonary fibrosis in mice. To induce an effective immune response, antigen-presenting cells have to not only present antigenic peptide with MHC molecules to T lymphocytes, but also express B7 costimulating molecules. The purpose of this study is to investigate whether B7 family costimulating molecules and interleukin-12 (IL-12), which primarily promote cellular immunity, are associated with anti-Fas antibody-induced pulmonary fibrosis.


METHODS
We examined the expression of B7-1, B7-2, and IL-12 using the revese transcription-polymerase chain reaction (RT-PCR), RT-in situ PCR, and immunohistochemistry.


RESULTS
We observed the upregulation of B7-1, B7-2, and IL-12 p40 mRNA after anti-Fas antibody inhalation. B7-2 and IL-12 p40 mRNA appeared to be expressed in mononuclear cells, while B7-1 mRNA and protein were expressed in bronchiolar epithelial cells as well as macrophages.


CONCLUSIONS
These findings indicate that the T-cell-mediated immune response in this model involved the upregulation of B7-1, B7-2, and IL-12, and that the aberrant expression of B7-1 in bronchiolar epithelial cells may induce autoreactive T cell proliferation against themselves.
Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, Fukuoka, Japan. kkuwano@kokyu.med.kyushu-u.ac.jp
K
K
Kuwano
Y
Y
Kaneko
N
N
Hagimoto
M
M
Kawasaki
R
R
Kunitake
T
T
Tanaka
T
T
Maeyama
H
H
Miyazaki
T
T
Matsuba
N
N
Hara
D000280:Administration, Inhalation; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000009:adverse effects; D015703:Antigens, CD / Q000235:genetics*; D017209:Apoptosis / Q000502:physiology; D018122:B7-1 Antigen / Q000235:genetics*; D051940:B7-2 Antigen; D001980:Bronchi / Q000166:cytology; D004847:Epithelial Cells / Q000737:chemistry / Q000166:cytology; D053222:Fas Ligand Protein; D007150:Immunohistochemistry; D018664:Interleukin-12 / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008813:Mice, Inbred ICR; D011658:Pulmonary Fibrosis / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000906:Antibodies; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D018664:Interleukin-12