title: [Effects and mechanisms of Notch signaling pathway on immune imbalance in chronic obstructive pulmonary disease].
abstract: Objective:To explore the role of Notch signaling pathway on immune imbalance in chronic obstructive pulmonary disease (COPD).Methods:Thirty BALB/c mice were randomly assigned into the healthy control group, COPD group, and COPD Gamma secretase inhibitors (GSI) group. Cigarette smoke exposure was used to establish the COPD model. T cells were enriched by filtering through nylon wool columns. The proportion of spleen-derived T-lymphocyte subsets was detected by flow cytometry. Real-time quantitative polymerase chain reaction (RT-PCR) and Western blot (WB) were used to detect the expression of splenic T cells' Notch1 and its downstream Hes1 mRNA and protein respectively.Results:The percentage of Th1, Th17 and Treg cells in CD4＋T cells of COPD mice (13.20±0.95, 10.22±0.45, 0.41±0.09)% were significantly increased compared with the healthy control group (8.07±0.44, 5.98±0.26, 0.26±0.05)%(allP<0.01). The proportion of Th1 and Th17 cells in COPD GSI group mice (9.48 ± 0.66, 7.70 ±0.39)% were significantly reduced compared with COPD group (allP<0.01). Ratio of Th1/Th2 in COPD group (18.70±4.12) was significantly increased compared with the healthy control group (12.63±1.91) (P<0.01), the percentage of Th17 and Treg in CD4＋T cell increased 71% and 58% respectively. GSI decreased the ratios of Th1/Th2 and Th17/Treg (allP<0.01). Notch1 receptor and its downstream Hes1 mRNA expression (5.15±0.77, 1.92±0.32) and protein expression (0.85±0.04, 0.16±0.02) of COPD mice were significantly increased compared with the healthy group respectively [(1.00 ± 0.00, 1.00 ± 0.00) and (0.17±0.01, 0.09±0.01)] (allP<0.01). GSI significantly inhibited the expression of mRNA and protein in Notch1 and its downstream Hes1 (allP<0.01). Notch1 and Hes1 mRNA and protein expressions were correlated positively with Th1 and Th17 cells and negatively correlated with Th2 and Treg cells in COPD group(allP<0.05).Conclusion:In COPD mice, there was T-lymphocyte subsets imbalance, such as the increased of Th1, Th17 proinflammatory cells, Notch1 and its downstream Hes1 mRNA and protein levels were increased, and was associated with T-lymphocyte subsets imbalance. GSI could partially inhibit Notch1, Hes1 expression and Th1 and Th17 cells, and thus Notch signaling pathway was involved in the immune disorder of COPD mice.
authors.affiliation: Department of Gerontal Respiratory Medicine, the First Hospital of Lanzhou University, Lanzhou 730000, China.
authors.forename: X N
authors.initials: XN
authors.lastname: Yang
authors.forename: X J
authors.initials: XJ
authors.lastname: Liu
authors.forename: L T
authors.initials: LT
authors.lastname: Zhao
authors.forename: X L
authors.initials: XL
authors.lastname: Zeng
authors.forename: H R
authors.initials: HR
authors.lastname: Bao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes; D016022:Case-Control Studies; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D029424:Pulmonary Disease, Chronic Obstructive / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000502:physiology; D058504:Th17 Cells / Q000187:drug effects*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D012333:RNA, Messenger; D051880:Receptors, Notch; D014028:Tobacco Smoke Pollution