Immune Mechanisms of Pulmonary Fibrosis with Bleomycin

Int J Mol Sci. 2023 Feb 5;24(4):3149. doi: 10.3390/ijms24043149.

Abstract

Fibrosis and structural remodeling of the lung tissue can significantly impair lung function, often with fatal consequences. The etiology of pulmonary fibrosis (PF) is diverse and includes different triggers such as allergens, chemicals, radiation, and environmental particles. However, the cause of idiopathic PF (IPF), one of the most common forms of PF, remains unknown. Experimental models have been developed to study the mechanisms of PF, and the murine bleomycin (BLM) model has received the most attention. Epithelial injury, inflammation, epithelial-mesenchymal transition (EMT), myofibroblast activation, and repeated tissue injury are important initiators of fibrosis. In this review, we examined the common mechanisms of lung wound-healing responses after BLM-induced lung injury as well as the pathogenesis of the most common PF. A three-stage model of wound repair involving injury, inflammation, and repair is outlined. Dysregulation of one or more of these three phases has been reported in many cases of PF. We reviewed the literature investigating PF pathogenesis, and the role of cytokines, chemokines, growth factors, and matrix feeding in an animal model of BLM-induced PF.

Keywords: bleomycin; chemokines; cytokines; growth factors; idiopathic pulmonary fibrosis; inflammation; pulmonary fibrosis; wound healing.

Publication types

  • Review

MeSH terms

  • Animals
  • Bleomycin
  • Disease Models, Animal
  • Epithelial-Mesenchymal Transition
  • Fibrosis
  • Idiopathic Pulmonary Fibrosis* / pathology
  • Inflammation / pathology
  • Lung / pathology
  • Lung Injury* / pathology
  • Mice

Substances

  • Bleomycin

Grants and funding

This study was financially supported in part by Grants-in-Aid for Scientific Research (B, 20H03957, Y.I.), (C, 21K06966, N.M.) and (B, 22H03366, T.K.) from Japan Society for the Promotion of Science (JSPS).