[Effects of in vivo instillation of genes coding for cytokines on pulmonary fibrosis].
Interstitial pneumonia is characterized by alveolitis that results in interstitial fibrosis. To study the role of humoral factors in the pathogenesis of interstitial fibrosis, we introduced expression vectors into Wistar rats via the trachea, to cause local overexpression of these humoral factors in the lung. Genes for human interleukin (IL)-6 and for the IL-6 receptor caused lymphocytic alveolitis without marked proliferation of fibroblasts. In contrast, overexpression of the genes for human transforming growth factor (TGF)-beta 1 and for human platelet-derived growth factor (PDGF)-B caused only mild cellular infiltration in the alveoli. However, both caused marked proliferation of fibroblasts and deposition of collagen fibrils. Introducing an expression vector that coded for a mutant form of the PDGF beta receptor that lacks its cytoplasmic domain markedly alleviated the pathohistologic changes caused by bleomycin in murine lungs. These findings show that TGF- and PDGF-B may be closely related to fibrosis in the lung, and that artificial regulation of them may be effective for treatment of lung fibrosis.
Hayashi
S
S
Department of Medicine III, Osaka university medical school.
Yoshida
M
M
Sakuma-Mochizuki
J
J
D000818:Animals; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D011658:Pulmonary Fibrosis / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D018121:Receptors, Cytokine / Q000235:genetics*; D011995:Recombination, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics
D015850:Interleukin-6; D010982:Platelet-Derived Growth Factor; D018121:Receptors, Cytokine; D016212:Transforming Growth Factor beta