TY - JOUR
T1 - The effects of treatment with cyclophosphamide and methylprednisolone on expression of endothelin-1 in unilateral instillation of paraquat-induced pulmonary fibrosis in guinea pigs
AU - So Ra Lee, Ra Lee
AU - Hye Cheol Jeong, Cheol Jeong
AU - Kyung Kyu Kim, Kyu Kim
AU - Sang Youb Lee, Youb Lee
AU - Sin Hyung Lee, Hyung Lee
AU - Jae Youn Cho, Youn Cho
AU - Jae Jeong Shim, Jeong Shim
AU - Kwang Ho In, Ho In
AU - Jong Sang Choi, Sang Choi
AU - Se Hwa Yoo, Hwa Yoo
AU - Kyung Ho Kang, Ho Kang
PY - 1999
Y1 - 1999
N2 - Background: The herbicide paraquat can cause severe lung injury and fibrosis in experimental animals. In this study we have investigated the changes in lung endothelin-1(Et-1) levels and immunohistochemical localization in relation to treatment with cyclophosphamide and methylprednisolone in paraquat induced pulmonary fibrosis in guinea pigs. Material and methods: 29 male Hartley guinea pigs were divided into 4 groups. Group I was normal control. Paraquat was instilled into the lung of guinea pig of group II, III and IV unilaterally. Group II was treated with cyclophosphamide and methylprednisolone. Group III was treated with methylprednisolone. Group IV was not treated. The degree of fibrosis was evaluated by H-E stains and Masson's trichrome stains and cell activity was assessed by Et-1 immunohistochemical stains. Statistical evaluation was performed using the Kruskawallis one-way analysis. Results: Paraquat induced an increase in numbers of fibroblasts and total amount of lung collagen in Group IV compared to the normal controls. There was no significant difference in total numbers of fibroblasts between any of paraquat instilled groups, but there was significant increase in total amount of collagen in Group IV compared to group II and III (p<0.05). The treatment of cyclophosphamide and methylprednisolone suppressed the growths of both fibroblasts and collagen, but this suppression was stastically significant only in the case of collagen. Et-1 immunoreactivities of bronchial epithelium, type II pneumocytes, endothelial cells and fibroblast in group II and III were decreased compared to those in group IV. Conclusion: These results demonstrate that Et-1 is an important contributing factor in the pathogenesis of pulmonary fibrosis. Et-1 is synthesized and released by bronchial epithelium, Type II pneumocyte, endothelial cells, alveolar macrophages and fibroblasts. Especially they are associated with alveolar macrophage and fibroblasts. We conclude that combined therapy of cyclophosphamide and methylprednisolone are more effective in the control of Et-1 expression and collagen deposition.
AB - Background: The herbicide paraquat can cause severe lung injury and fibrosis in experimental animals. In this study we have investigated the changes in lung endothelin-1(Et-1) levels and immunohistochemical localization in relation to treatment with cyclophosphamide and methylprednisolone in paraquat induced pulmonary fibrosis in guinea pigs. Material and methods: 29 male Hartley guinea pigs were divided into 4 groups. Group I was normal control. Paraquat was instilled into the lung of guinea pig of group II, III and IV unilaterally. Group II was treated with cyclophosphamide and methylprednisolone. Group III was treated with methylprednisolone. Group IV was not treated. The degree of fibrosis was evaluated by H-E stains and Masson's trichrome stains and cell activity was assessed by Et-1 immunohistochemical stains. Statistical evaluation was performed using the Kruskawallis one-way analysis. Results: Paraquat induced an increase in numbers of fibroblasts and total amount of lung collagen in Group IV compared to the normal controls. There was no significant difference in total numbers of fibroblasts between any of paraquat instilled groups, but there was significant increase in total amount of collagen in Group IV compared to group II and III (p<0.05). The treatment of cyclophosphamide and methylprednisolone suppressed the growths of both fibroblasts and collagen, but this suppression was stastically significant only in the case of collagen. Et-1 immunoreactivities of bronchial epithelium, type II pneumocytes, endothelial cells and fibroblast in group II and III were decreased compared to those in group IV. Conclusion: These results demonstrate that Et-1 is an important contributing factor in the pathogenesis of pulmonary fibrosis. Et-1 is synthesized and released by bronchial epithelium, Type II pneumocyte, endothelial cells, alveolar macrophages and fibroblasts. Especially they are associated with alveolar macrophage and fibroblasts. We conclude that combined therapy of cyclophosphamide and methylprednisolone are more effective in the control of Et-1 expression and collagen deposition.
KW - Cyclophosphamide
KW - Endothelin-1
KW - Methylprednisolone
KW - Paraquat
KW - Pulmonary fibrosis
UR - http://www.scopus.com/inward/record.url?scp=0032849843&partnerID=8YFLogxK
U2 - 10.4046/trd.1999.46.6.775
DO - 10.4046/trd.1999.46.6.775
M3 - Article
AN - SCOPUS:0032849843
SN - 0378-0066
VL - 46
SP - 775
EP - 785
JO - Tuberculosis and Respiratory Diseases
JF - Tuberculosis and Respiratory Diseases
IS - 6
ER -