Fig. 1.

NETs induce pulmonary fibrosis through fibroblasts. PMA, Bleomycin, CSE could promote the release of NETs from neutrophils. Under hypoxia conditions, REDD1 promotes NETs release by enhancing autophagy, while Cl-amidine (a PAD4 inhibitor) and DNase prevent NETs production and action process. It has been suggested that MPO and Histones contribute to the proliferation and differentiation of fibroblasts, whereas DNA promotes myofibroblast differentiation by connecting with the pathway TLR9-miR-7-SMAD2. There is evidence that IL-17, IL17A, and TF promote fibrotic activity in differentiated fibroblasts, but not their differentiation. NETs: neutrophil extracellular traps; PMA: phorbol 12-myristate 13-acetate; CSE: cigarette smoke extract; PAD4: peptidylarginine deiminase type 4; MPO: myeloperoxidase