Rapamycin attenuates pulmonary allergic vasculitis in murine model by reducing TGF-β production in the lung.
BACKGROUND
Rapamycin has been reported to inhibit mesenchymal cell proliferation in a murine model of pulmonary fibrosis. In the present study, we examined the effects of rapamycin on vascular remodeling including intraluminal myofibroblast proliferation in a murine model of allergic vasculitis with eosinophil infiltration.


METHODS
C57BL/6 mice were sensitized with ovalbumin (OVA) and alum. The positive controls were exposed to aerosolized OVA daily for 7 days. The other group of mice was administered with rapamycin (1mg/kg) intraperitoneally, in parallel with daily exposure to aerosolized OVA for 7 days. On the 3rd and 7th day, bronchoalveolar lavage (BAL) was performed and the lungs were excised for pathological analysis. Cell differentials were determined and concentrations of IL-4, IL-5, IL-13 and TGF-β in the BAL fluid (BALF) were measured. Semi-quantitative analysis of pathological changes in the pulmonary arteries was evaluated according to the severity of vasculitis.


RESULTS
The number of eosinophils in BALF was reduced significantly in the mice treated with rapamycin compared to the positive control. There was a significant decrease in the TGF-β concentration of the BALF in the rapamycin-treated group compared to that of the positive control. The pathological scores were reduced significantly in the rapamycin-treated group compared to the positive control group. Intraluminal myofibroblasts in pulmonary arteries were reduced dramatically in the rapamycin-treated group compared to the positive control group.


CONCLUSIONS
Rapamycin suppressed pulmonary vascular remodeling in a murine model of allergic vasculitis with eosinophil infiltration through reducing eosinophil infiltration and TGF-β production in the lung and inhibition against biological action of TGF-β.
Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Iwate, Japan.
Rumi
R
Koizumi
Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Iwate, Japan.
Nobuhito
N
Sasaki
Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Iwate, Japan.
Yutaka
Y
Nakamura
Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Iwate, Japan.
Naomi
N
Suzuki
Department of Pathology, Iwate Medical University School of Medicine, Iwate, Japan.
Takashi
T
Sawai
Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Iwate, Japan.
Kohei
K
Yamauchi
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D004804:Eosinophils / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008171:Lung Diseases / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D058628:Myofibroblasts / Q000187:drug effects / Q000502:physiology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000473:pathology; D020123:Sirolimus / Q000008:administration & dosage*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D066253:Vascular Remodeling / Q000187:drug effects*; D014657:Vasculitis / Q000188:drug therapy* / Q000276:immunology
D007166:Immunosuppressive Agents; D016212:Transforming Growth Factor beta; D020123:Sirolimus