Abstract
Introduction: Although the etiology of an acute exacerbation of idiopathic pulmonary fibrosis (IPF) is unknown, it may be represented by a clinically occult but biologically distinct condition that often remains undiagnosed, such as viral infections. Unmethylated CpG motifs present in both bacterial and viral DNA initiate an innate immune response mediated by Toll-like receptor 9 (TLR9). We examined the inflammatory response to the intratracheal injection of CpG dinucleotides (CpG-ODN) in bleomycin (BLM)-induced lung fibrosis in mice.
Methods: Lung fibrosis was induced in female C57BL/6 mice by the intraperitoneal injection of BLM. Twenty-eight days after the injection of either BLM or saline, the mice received intratracheal injections of either saline or CpG-ODN. A total number of 4 groups (saline; BLM; saline/CpG; BLM/CpG) were investigated. After 24 h, the mice were killed, and the neutrophil counts and cytokine levels were determined in the bronchoalveolar lavage fluid (BALF).
Results: There were no differences in the neutrophil counts between the saline and BLM groups. The neutrophil counts in the BLM/CpG group were significantly higher than those in the saline/CpG group. The levels of macrophage inflammatory protein (MIP)-2 and interleukin (IL)-6 in the BALF were found to be significantly higher in the BLM/CpG group than in the saline/CpG group. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemical analysis of the lung tissue revealed an upregulation of TLR9 expression induced by BLM administration.
Conclusion: These results suggest that the TLR9-mediated lung inflammatory responses are enhanced in BLM-induced lung fibrosis in mice.
- © 2011 ERS
