Expression and pathological significance of CC chemokine receptor 7 and its ligands in the airway of asthmatic rats exposed to cigarette smoke

Abstract

Background: Cigarette smoking aggravates the symptoms of asthma, leading to the rapid decline of lung function. Dendritic cells (DCs) and lymphocytes are considered initiating and promoting factors for the airway inflammation reactions of asthma. In addition, activation of CC chemokine receptor 7 (CCR7) by chemokine (C-C motif) ligand (CCL) 19 and 21 promotes DCs and T cells migration to lymphoid tissues during inflammation. We aimed to examine how cigarette smoke affects the expression of CCR7 in the lungs of asthmatic rats and explore the signaling mechanism linking CCR7 expression to exacerbation of symptoms. Methods: Forty Wistar rats were randomized to four groups: control, asthma, smoke exposure, and asthma with smoke exposure groups. A rat asthma model was established by intraperitoneal ovalbumin injection. CCR7 expression was examined with immunohistochemistry and western blotting. The number of airway DCs was determined by OX62 immunohistochemistry. Interferon (INF)-γ, interleukin (IL)-4, CCL19, and CCL21 expression levels in blood and bronchioalveolar lavage fluid (BALF) were determined by enzymelinked immunosorbent assays (ELISAs). Results: Tissue CCR7 expression, peripheral blood and BALF CCL19 and CCL21 concentrations, and the number of airway DCs were significantly higher in the asthma with smoke exposure group than the asthma group (P<0.01). In addition, INF-γ expression was decreased and IL-4 increased in the asthma and asthma with smoke exposure groups compared with the control group (P<0.01), and in the asthma with smoke exposure group compared with the asthma group (P<0.01). Expression of CCR7 correlated negatively with INF-γ expression in peripheral blood and BALF (P<0.01), and positively with the airway DCs and IL-4 expression in the peripheral blood and BALF (P<0.01). Conclusions: Cigarette smoking may aggravate asthma symptoms by attenuating immunity, possibly through CCR7-mediated DCs aggregation in lung tissue.

The Significance of the Alter miR let-7a and miR-335 Expression Level Regulating the CCR7/CCL19 Axis as Potential Biomarkers of Tumor Progression in NSCLC

“…It was found that smoking may correlate with elevated CCR7 mRNA expression level [26], that CCR7 plays a major role in modulating inflammatory responses in airways in pulmonary diseases [27], and that cigarette smoking upregulates CCR7, CCL19, and CCL21 mRNA expression levels in lymph nodes of wild-type mice [28]. It was also concluded that exposure to cigarette smoke can upregulate the number of DCs and cause immunoreactions through CCR7mediated chemotaxis [29]. Surpassingly, in the NSCLC patients in the present study, higher CCR7 and CCL19 expression levels were observed in non-smokers than in smokers; indeed, cigarette smoke extract (CSE) was found to suppress CCR7 expression on DCs in the lungs of smokers, but not diminish their migration towards a CCR7 ligand [28].…”

Single-cell multi-ome regression models identify functional and disease-associated enhancers and enable chromatin potential analysis

“…One such variant is rs112401631 (chr17:40608272:T:A), a fine-mapped variant for asthma (PIP = 0.27) that colocalizes with an eQTL chr17:40600717:G (PP.H4 = 0.9022; coloc 23 ) linked to CCR7 gene in the lymphoblastoid cell line 23 , 24 . The CCR7 gene is well-known for its role in the homing of T cell populations to lymphoid organs 25 , 26 , and CCR7 + memory CD4 + T cells have previously been associated with severity of asthma 27 , 28 . In PBMC data, the tile underlying rs112401631 was predicted to be significantly linked to the CCR7 gene in various T cell subtypes (CD8 effector with FDR-adjusted P = 3.7 × 10 −08 , CD4 memory with FDR-adjusted P = 5.9 × 10 −21 , CD8 naive with FDR-adjusted P = 7.6 × 10 −18 and CD4 naive with FDR-adjusted P = 2.2 × 10 −17 ; Fig.…”

Water-Pipe Smoking Exposure Deregulates a Set of Genes Associated with Human Head and Neck Cancer Development and Prognosis

“…Similar to our data, CCL4 expression is linked with poor prognosis in cancer [ 45 ]. On the other hand, cigarette smoking has been shown to increase blood and bronchoalveolar lavage fluid levels of the CCR7 ligands CCL19 and CCL21 [ 46 ], thereby contributing to migration of lung cancer cells [ 47 ]. Additionally, previous research has considered CCL21 in oral cancer as a candidate marker for unfavorable outcome [ 48 ].…”