Fig. 1

Potential mechanism of AE-PF in animal models

The mechanism of AE-PF possibly driven by the stress of viruses, bacteria and other agents, such as LPS and small molecule compounds is focused on the enhanced apoptosis of AEC2, excessive inflammation and extracellular matrix deposition. Firstly, the stresses of infection and other challenging agents may promote the secretion of chemokines CCL2 and CCL12 of AEC2 and AMs, leading to increased recruitment of circulating fibrocytes and deposition of extracellular matrix. Additionally, it upregulates the expressions of pro-inflammatory cytokines TNF-α, IL-6, and IL-17 A of AEC2 and CD4⁺ T cells, while inhibits the production of IFN. Furthermore, the challenging agents can increase the expressions of IL-1, IL-18, NO, and Mincle of AMs, and lead to the excessive inflammation. Secondly, the stress may augment the expressions of TGF-β receptor 1 on AEC2, activate SMAD3 phosphorylation. Some pathogens may also produce small molecule substances which result in pore-like damage on the surface of AEC2, provoke caspase 3 activation, Bcl2 upregulation and Bax downregulation, ultimately causes the enhanced apoptosis of AEC2

Abbreviations: AE: acute exacerbation; AE-PF: acute exacerbations of pulmonary fibrosis; AEC2: type II alveolar epithelial cells; AMs: alveolar macrophages; BLM: bleomycin; ERS: endoplasmic reticulum stress; ECM: Extracellular matrix; HSV1: Herpes simplex virus 1; γHV-68: γ-Herpesvirus -68; LPS: lipopolysaccharide; NO: nitric oxide; Spn: Streptococcus pneumoniae; IFN: interferon