Intratracheal instillation of polyacrylic acid induced pulmonary fibrosis with elevated transforming growth factor-ß1 and connective tissue growth factor.

ABSTRACT

We investigated the intratracheal instillation of Polyacrylic acid (PAA) in rats to determine if it would cause pulmonary disorders, and to see what factors would be associated with the pathological changes. Male F344 rats were intratracheally instilled with low (0.2 mg/rat) and high (1.0 mg/rat) doses of PAA. They were sacrificed at 3 days, 1 week, 1 month, 3 months, and 6 months after PAA exposure to examine inflammatory and fibrotic changes in the lungs. There was a persistent increase in the neutrophil count, lactate dehydrogenase (LDH) levels, cytokine-induced neutrophil chemoattractant (CINC) values in bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in lung tissue. Transforming growth factor-beta 1 (TGF-ß1), a fibrotic factor, showed a sustained increase in the BALF until 6 months after intratracheal instillation, and connective tissue growth factor (CTGF) in lung tissue was elevated at 3 days after exposure. Histopathological findings in the lung tissue showed persistent (more than one month) inflammation, fibrotic changes, and epithelial-mesenchymal transition (EMT) changes. There was also a strong correlation between TGF-ß1 in the BALF and, especially, in the fibrosis score of histopathological specimens. Intratracheal instillation of PAA induced persistent neutrophilic inflammation, fibrosis, and EMT in the rats' lungs, and TGF-ß1 and CTGF appeared to be associated with the persistent fibrosis.