IL-17A Mediated Downstream Changes During Acute Lung Injury

Abstract

Acute lung injury is the severe health issue characterized by inflammation in the airways results in the alteration of alveolar architecture. The inflammatory phase usually mediated by the neutrophil accumulation, migration of macrophages, alveolar infiltration and cytokines activation. IL-17A is a class of pro-inflammatory cytokines elevated during the initial phase of injury. IL-17A mediation could alter various pathways such as, alveolar epithelial cells (AECs) apoptosis, chemokines enhancement and excitation as well as other proliferatory pathways. IL-17A mediated activation of chemokines expression is one of the key phenomenon promotes the inflammatory process. IL-17A mediated downstream modulation leads to the severe form of injury, which causes the significant loss of AECs. The severe loss of AECs stimulates the conversion of fibroblasts to myofibroblasts and deposition of extracellular matrix (ECM). The excess deposition of ECM at the alveolar epithelial barrier causes the thickening of alveolar epithelium and results in the progression of lethal, irreversible disease called pulmonary fibrosis.

Proteomics Analysis Revealed the Importance of Inflammation-Mediated Downstream Pathways and the Protective Role of Curcumin in Bleomycin-Induced Pulmonary Fibrosis in C57BL/6 Mice

“…BLM is a well-known chemotherapeutic drug, which has side effects . BLM causes DNA damage and is involved in the elaboration of inflammatory cytokines within the alveolar space. , According to recent literature, BLM could be an effective model to study the pathophysiology of the lungs. ,, The pulmonary inflammation is characterized by the influx of inflammatory cell migration, macrophage infiltration, and elaboration of inflammatory cytokines and chemokines. , The processes of production and migration of inflammatory cells are mediated through the blood . Blood acts as a major parameter in terms of early diagnosis of the diseases.…”

“…13,29 According to recent literature, BLM could be an effective model to study the pathophysiology of the lungs. 1,8,29 The pulmonary inflammation is characterized by the influx of inflammatory cell migration, macrophage infiltration, and elaboration of inflammatory cytokines and chemokines. 30,31 The processes of production and migration of inflammatory cells are mediated through the blood.…”

“…It is reported that the administration of bleomycin (BLM) promotes the elaboration of inflammatory cytokines, accumulation of macrophages, and alveolar epithelial cells (AEC) apoptosis by causing DNA damage to the AECs. ,, BLM-induced inflammation is mediated by IL-17A, which in turn modulates the p53-fibrinolytic pathway components to take part in the progression of pulmonary fibrosis. , IL-17A is a major pro-inflammatory cytokine known to modulate the expression of certain chemokines, pro-inflammatory cytokines, fibrinolytic system components, and antimicrobial peptides in the airway epithelial cells to support the host defense mechanism . The studies reported that the specific receptor for IL-17A is most abundantly found in nonhematopoietic cells such as epithelial and fibroblast cells …”