Late Stage of Experimental Pulmonary Fibrosis is Modulated by Collagen V

Abstract

Background: The late phase of experimental models of pulmonary fibrosis (PF) tend to recover from fibrotic process, but in different degrees depending on the drug/strain/inflammation. The mechanisms which prolong the process in the late phase in certain strains may participate in the PF. Aim: To determine the immune-fibrotic pattern in pulmonary fibrosis models in the late stage (21 days). Methods: The PF was induced in Bleomycin (BLM-BALB) and Paraquat (PQ-BALB) Balb/c and IL17-RA-Knockout (BLM-IL17KO-C57) and wild C57/B6 (BLM-C57). We used the picrosirius-polarization method and immunofluorescence to morphometrically study peribronchiolar (PB) and peripherical (PP) collagen fibers and collagen III and V, respectively. The results of collagens were confirmed by RT-PCR of cultured pulmonary fibroblasts. Results: The late PQ and BLM-mediated peribronchiolar fibrosis is IL-17 independent, as IL17-RA)/) mice developed similar PB after induction when compared to BLM-BALB, PQ-BALB and BLM-C57. The level of gene expression of collagen I and III did not show differences between the groups of the cultures, validating our results. However, the PP was higher in the C57BL/6, independent of the absence of IL-17RA. The protein expression of Col5 was higher in IL-17RA-KO and lower in BLM-Balb/c. Like-wise, the gene expression of Col5 was higher in IL17RA-KO and lower in BLM-Balb/c. Conclusion: The perpetuation of PF in fibrosis-susceptible mice can be modulated by Col5 in a IL-17ReceptorA-independent manner in the late phase. However, the IL-17 pattern appears to influence the expression of collagen V. This suggests that exposure of the collagen V from the basement membrane is an important component responsible for PF.