The role of Cold‐Inducible RNA‐binding protein in respiratory diseases

Abstract

Cold‐inducible RNA‐binding protein (CIRP) is a stress‐response protein that is expressed in various types of cells and acts as an RNA chaperone, modifying the stability of its targeted mRNA. Intracellular CIRP could also be released into extracellular space and once released, extracellular CIRP (eCIRP) acts as a damage‐associated molecular pattern (DAMP) to induce and amplify inflammation. Recent studies have found that eCIRP could promote acute lung injury (ALI) via activation of macrophages, neutrophils, pneumocytes and lung vascular endothelial cells in context of sepsis, haemorrhagic shock, intestinal ischemia/reperfusion injury and severe acute pancreatitis. In addition, CIRP is also highly expressed in the bronchial epithelial cells and its expression is upregulated in the bronchial epithelial cells of patients with chronic obstructive pulmonary diseases (COPD) and rat models with chronic bronchitis. CIRP is a key contributing factor in the cold‐induced exacerbation of COPD by promoting the expression of inflammatory genes and hypersecretion of airway mucus in the bronchial epithelial cells. Besides, CIRP is also involved in regulating pulmonary fibrosis, as eCIRP could directly activate and induce an inflammatory phenotype in pulmonary fibroblast. This review summarizes the findings of CIRP investigation in respiratory diseases and the underlying molecular mechanisms.

Associations of cold‐inducible RNA‐binding protein with bacterial load, proinflammatory cytokines and mortality from pneumonia

“…Recent studies have epitomized that eCIRP can promote acute lung injury via activation of macrophages, neutrophils, pneumocytes, and lung vascular endothelial cells in the context of sepsis, hemorrhagic shock, intestinal ischemia/reperfusion injury, and severe acute pancreatitis. 19 Macrophage erythropoietin receptor signaling is impaired by eCIRP through Rab26 during acute lung injury/acute respiratory distress syndrome, leading to restrained M2 macrophage polarization and delayed resolution of inflammation. 20 Furthermore, eCIRP dysregulates macrophage bacterial phagocytosis during sepsis.…”

Extracellular cold-inducible RNA-binding protein mediated neuroinflammation and neuronal apoptosis after traumatic brain injury

“…There are two different forms of CIRP: intracellular CIRP and eCIRP. Currently, increasing evidence has indicated that eCIRP is critically involved in the development of inflammatory diseases [ 13 , 14 ]. It is likely that eCIRP is associated with alcohol-, haemorrhage- and cerebral ischaemia-induced brain inflammation [ 15–18 ].…”

Cold-inducible RNA-binding protein induces inflammatory responses via NF-κB signaling pathway in normal human bronchial epithelial cells infected with streptococcus pneumoniae

“…As an endogenous in ammatory factor, CIRP directly induces the upregulation of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and other pro-in ammatory cytokines in serum, thereby initiating a cascade reaction of in ammation and exacerbating tissue injury [12,13]. Recent studies have indicated the involvement of CIRP in the pathogenesis of various respiratory diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary brosis (IPF), and acute respiratory distress syndrome (ARDS)/ acute lung injury (ALI) [14,15]. The expression of CIRP is signi cantly elevated in bronchial epithelial cells, both in patients with chronic obstructive pulmonary diseases (COPD) and in rat models with chronic bronchitis [16].…”