Inhibition of C-X-C Motif Chemokine 10 (CXCL10) Protects Mice from Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease

Abstract

BackgroundChronic obstructive pulmonary disease (COPD) is a type of obstructive lung disease characterized by long-term breathing problems and poor airflow. COPD can progress to persistent decline of pulmonary function. This study explored the effect of CXCL10 on COPD induced by cigarette smoke (CS) and its underlying mechanism.Material/MethodsWild-type (WT) mice were randomly assigned into 3 groups: the control group, the CS group, and the intervention group. Mice in the CS group were exposed to CS and mice in the CXCL10 group were exposed to CS and CXCL10 neutralizing antibody. At 24 h after the last CS exposure, body weight and lung functions of each mouse were recorded. Mice were then anesthetized for collecting bronchoalveolar lavage fluid (BALF) and lung tissues. Levels of interleukin-6 (IL-6), keratinocyte chemotactic factor (KC), and monocyte chemoattractant protein-1 (MCP-1) in supernatant and lung homogenate were detected by ELISA and real-time PCR (RT-PCR), respectively. For in vitro experiments, human bronchial epithelial cells 16HBE were stimulated with different concentrations of cigarette smoke extract (CSE) and CXCL10. Cell viability and levels of inflammatory cytokines in the cell supernatant were detected by Cell Counting Kit-8 (CCK-8) and ELISA assay, respectively.ResultsOur data showed significant weight loss and reduction of lung functions in mice in the CS group compared with those in the control group and intervention group. Increased levels of IL-6, KC, and MCP-1 in BALF and lung homogenate were observed in mice in the model group compared to those in the control group and intervention group. In vitro experiments also confirmed that CXCL10-neutralizing antibody can inhibit CSE-induced cell necrosis and activation of inflammatory cytokines.ConclusionsInhibited CXCL10 protects against COPD progression by decreasing secretion of inflammatory factors, which provides a new direction for the clinical prevention and treatment of COPD.

Immune modulation by chronic exposure to waterpipe smoke and immediate-early gene regulation in murine lungs

“…CXCL10 and CXCL9 are chemokines produced in response to CS. They bind to receptors that are mainly expressed on T lymphocytes, powerfully attracting other cells from the innate and adaptive immunity 51–54. CCL11 attracts eosinophils that are important for the development of lung airway hyper-responsiveness in asthma and allergies 55.…”

Baicalin Exerts Anti‐Airway Inflammation and Anti‐Remodelling Effects in Severe Stage Rat Model of Chronic Obstructive Pulmonary Disease

“…Studies showed that IL-10 level was decreased in COPD patients while healthy volunteers expressed higher level of IL-10 [ 36 ]. Therefore, lung function and inflammation can be improved by decreasing inflammatory factors [ 37 ]. Tregs were differentiated for ameliorating inflammatory effect through TGF- β 1 in COPD against the Th17 proinflammatory effect, preserving inflammation balance [ 32 ].…”

Chemokines in COPD: From Implication to Therapeutic Use

“…Targeting CXCL10 seems an interesting option. An in vitro study has shown that CXCL10-neutralizing antibody can inhibit CSE-induced cell necrosis and activation of inflammatory cytokines in the 16HBE cell line [79]. In the same study, mice treated with CXCL10 neutralizing antibody did not develop COPD features (weight loss; reduction of lung function, increased levels of IL-6, and CCL2 in BALF and lung homogenate) as compared to cigarette smoke-exposed mice.…”