TGFβ/Smad mediated the polyhexamethyleneguanide areosol-induced irreversible pulmonary fibrosis in subchronic inhalation exposure.

AIM

Polyhexamethylene guanidine (PHMG) is widely used as a disinfectant with broad spectra of bactericidal activity and low oral toxicity. However, inhalation of PHMG can cause pulmonary injury and severe pulmonary fibrosis. The mechanism underlying PHMG aerosol induced pulmonary fibrosis remains unclear. In this study, we aimed to examine the subchronic lung injury and determine potential cytokines involved in PHMG aerosol induced fibrosis.

METHODS

C57BL/6N mice were exposed to 1.03 mg/m PHMG through aerosol inhalation for 3 weeks, or 3 weeks followed by other 3 weeks recovery.

RESULTS

The results indicated that the expression of transforming growth factor-beta1 (TGF-β1) and extracellular matrix remodeling markers were up-regulated in the PHMG-treated mice and these parameters were aggravated after 3 weeks recovery. Bronchoalveolar lavage fluids (BALFs) analysis showed that the number of total cells was significantly decreased in exposure group. The percentage of macrophages in BALFs decreased significantly whereas the percentage of neutrophils and lymphocytes increased. Extensive collagen deposition was observed in the peribronchiolar and interstitial areas in the PHMG exposed lungs.

CONCLUSION

In conclusion, even low-does PHMG aerosol exposure could induce mice pulmonary local inflammation and irreversible fibrosis. In addition, TGF-β/Smad signaling pathway mediated the extracellular matrix remodeling involved in the development of pulmonary fibrosis.