CC Chemokines in Idiopathic Pulmonary Fibrosis: Pathogenic Role and Therapeutic Potential

Abstract

Idiopathic pulmonary fibrosis (IPF), characterized by progressive worsening of dyspnea and irreversible decline in lung function, is a chronic and progressive respiratory disease with a poor prognosis. Chronic or repeated lung injury results in inflammation and an excessive injury-repairing response that drives the development of IPF. A number of studies have shown that the development and progression of IPF are associated with dysregulated expression of several chemokines and chemokine receptors, several of which have been used as predictors of IPF outcome. Chemokines of the CC family play significant roles in exacerbating IPF progression by immune cell attraction or fibroblast activation. Modulating levels of detrimental CC chemokines and interrupting the corresponding transduction axis by neutralizing antibodies or antagonists are potential treatment options for IPF. Here, we review the roles of different CC chemokines in the pathogenesis of IPF, and their potential use as biomarkers or therapeutic targets.

Fibrocytes enhance mammary gland fibrosis in obesity

“…CCL2‐CCR2 signaling is necessary for the recruitment of macrophages to adipose tissue in obesity, as loss of CCL2 or CCR2 signaling in null mice leads to a significant reduction in adipose tissue macrophages 16,31 . Emerging evidence suggests that increased levels of CCL2 are also associated with fibrosis in various organs, 32–34 leaving questions regarding the cells that are responding to CCL2 to induce this pathology 35 …”

“…16,31 Emerging evidence suggests that increased levels of CCL2 are also associated with fibrosis in various organs, [32][33][34] leaving questions regarding the cells that are responding to CCL2 to induce this pathology. 35 Myofibroblasts are one of the main cell types to contribute to extracellular matrix production and remodeling in multiple tissues. 36 Smooth muscle actin (SMA)-positive myofibroblasts were identified in breast tissue from patients with obesity and were nearly absent in breast tissue from lean patients.…”

P21 facilitates macrophage chemotaxis by promoting CCL7 in the lung epithelial cell lines treated with radiation and bleomycin

“…Chemokines, consisting of a large number of ligands and receptors, participate in the function and organization of the immune system [ 26 ]. To identify the critical signaling factors that may contribute to the chemotaxis of macrophages in the lung injury after different stresses, the expressions of some chemokines associated with monocytes, including CCL2 , CCL7 , CXCL5 , CXCL9 , CXCL10 , CXCL14 , and CXCL16 were examined in Beas-2B cells.…”

“…1 and 2 ). Actually, immune system could be initially activated to maintain microenvironment homeostasis of macrophages, lymphocytes and granulocytes, which was characterized by multiple immune cells infiltration and a series of cytokines and chemokines [ 26 ]. However, imbalance between inflammation and restoration responses contributes to the worsening of lung injury from pneumonitis to pulmonary fibrosis, and their potential biomarkers including inflammation-related factors (IL-1β, IL-6, IL-8, IL-10 and CRP) and fibrosis-related factors (TGF-β, ET-1, KL-6, and PAI-1) have been reviewed previously [ 27 ].…”

“…CCL7 was reported as one of inflammatory chemokines in the anti-infectious immunity, where monocytes, macrophages and neutrophils were recruited for viral clearance in the infected tissues and organs [ 26 ]. In addition, it was found that the overexpression of CCL7 in tumor cells could facilitate the anti-PD-1 therapy in lung cancer via recruiting DC1 cells into the tumor immune microenvironment [ 47 ].…”