Effects of sulforaphane on Toll-like receptor 4/myeloid differentiation factor 88 pathway of monocyte-derived macrophages from patients with chronic obstructive pulmonary disease
- Author:
- No author available
- Journal Title:
- Chinese Journal of Tuberculosis and Respiratory Diseases
- Issue:
- 4
- DOI:
- 10.3760/cma.j.issn.1001-0939.2014.04.004
- Key Word:
- 肺疾病,慢性阻塞性;Toll样受体4;髓样分化因子88;巨噬细胞;Pulmonary disease,chronic obstructive;Toll-like receptor 4;Myeloid differentiation factor 88;Macrophages
Abstract： Objective To explore the effects of sulforaphane on Toll-like receptor 4 (TLR4)/ myeloid differentiation factor 88 (MyD88) pathway and its downstream inflammatory cytokines in patients with chronic obstructive pulmonary disease (COPD).Methods From Jan.2012 to Mar.2013,thirty-two stable COPD patients and thirty healthy donors (non-COPD group) from the First Hospital of Lanzhou University were recruited.The peripheral blood monocytes were isolated and induced to macrophages (monocyte-derived macrophages,MDMs).The MDMs of COPD patients were divided into a blank control group,a LPS group,a sulforaphane group,a sulforaphane and LPS group (combined group),while the MDMs from the non-COPD group received no drug intervention.The number of cells in each group was 3 ×106.The mRNA and protein expression of TLR4 and MyD88 were measured with real-time PCR and Western blot.The TNF-α and IL-6 levels in the culture supernatant were measured with ELISA.Oneway ANOVA and LSD-t test were used for statistical analysis.Results The levels of mRNA and protein of TLR4 and MyD88 and the contents of TNF-α and IL-6 in the culture supernatant were higher in the blank control group [3.7 ±0.5,1.9±0.4,0.45 ±0.18,1.11 ±0.65,(31 ±4) and (43 ±5) μg/L] than those in the nonCOPDgroup [1.00,1.00,0.26±0.14,0.58±0.40,(19±2) and (29±4) μg/L] (t=2.19-12.11,P ＜0.05 or P ＜0.01).After LPS treatment (LPS group),the above parameters [5.5 ± 1.1,3.4 ± 1.6,0.65 ± 0.20,1.66 ± 0.64,(47 ± 4) and (54 ± 5) μg/L] were increased as compared to those in the blank control group (t =2.39-11.9,P ＜ 0.05 or P ＜ 0.01),but after sulforaphane treatment (Sulforaphane group),these parameters [2.2 ± 0.4,1.0 ± 0.6,0.25 ± 0.09,0.62 ± 0.34,(20 ± 3) and (27 ±4) μg/L] were decreased as compared to those in the blank control group (t =2.13-8.46,P ＜ 0.05 or P ＜ 0.01).Similarly,these parameters in the combined group [3.2 ± 0.5,1.5 ± 0.8,0.33 ± 0.11,0.77 ±0.25,(31 ±3) and (33 ±4) μg/L] were also remarkably decreased as compared to those in the LPS group (t =3.87-12.24,all P＜0.01).Conclusions The TLR4/MyD88 pathway was activated and its downstream inflammatory cytokines were increased in macrophages from COPD patients.Sulforaphane could inhibit the TLR4/MyD88 pathway and reduce the releasing of downstream inflammatory cytokines,suggesting that sulforaphane may have an anti-inflammatory effect in COPD.
- [1]吴航,况九龙.模式识别受体在慢性阻塞性肺疾病中的作用[J].2011,(10).
- [2]李雯,徐永健.脂多糖对慢性阻塞性肺疾病患者气道上皮细胞Toll样受体4表达的影响[J].2006,(7).
- [3]中华医学会呼吸病学分会慢性阻塞性肺疾病学组.慢性阻塞性肺疾病诊治指南（2007年修订版）[J].2007,(1).
- [4]Tudhope SJ,Finney Hayward TK,Wedzicha JA,etc.Defective macrophage phagocytosis of bacteria in COPD.[J].2010,35(5).
- [5]Liang Hao,Yuan QiPeng.Natural sulforaphane as a functional chemopreventive agent: including a review of isolation, purification and analysis methods.[J].2012,32(3).
- [6]Yang,X.,Wang,S.,Lin,N.,etc.Sulphoraphane inhibited the expressions of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 through MyD88-dependent toll-like receptor-4 pathway in cultured endothelial cells[J].2012,22(3).
- [7]Kim YS,Youn HS,Park Z.Sulforaphane suppresses oligomerization of TLR4 in a thiol-dependent manner.[J].2010,184(1).
- [8]Starrett W,Blake DJ.Sulforaphane inhibits de novo synthesis of IL-8 and MCP-1 in human epithelial cells generated by cigarette smoke extract.[J].2011,8(2).
- [9]Ren W,Hu L,Hua F,etc.Myeloid differentiation protein 2 silencing decreases LPS-induced cytokine production and TLR4/MyD88 pathway activity in alveolar macrophages.[J].2011,141(1).
- [10]Lisette IZ Kunz,Thérèse S Lapperre,Jiska B Snoeck-Stroband,etc.Smoking status and anti-inflammatory macrophages in bronchoalveolar lavage and induced sputum in COPD[J].2011,12(1).
- [11].Myeloid differentiation factor 88-dependent signaling is critical for acute organic dust-induced airway inflammation in mice[J].2013,48(6).
- [12]Geraghty P,Dabo AJ,D'Armiento J.TLR4 protein contributes to cigarette smoke-induced matrix metalloproteinase-1 (MMP-1) expression in chronic obstructive pulmonary disease.[J].2011,286(34).
- [13]Amoruso A,Gunella G,Rondano.Tobacco smoke affects expression of peroxisome proliferator-activated receptor-gamma in monocyte/macrophages of patients with coronary heart disease.[J].2009,158(5).
- [14]He,W.,Qu,T.,Yu,Q.,etc.LPS induces IL-8 expression through TLR4, MyD88, NF-kappaB and MAPK pathways in human dental pulp stem cells[J].2013,46(2).
- [15]Kanazawa H,Yamazaki T,Akagawa KS,etc.Functional heterogeneity of colony-stimulating factor-induced human monocyte-derived macrophages.[J].2006,11(Suppl.1).
- [16]Zhang M,Ding X,Zhou X,etc.Relevance of lower airway bacterial colonization, airway inflammation, and pulmonary function in the stable stage of chronic obstructive pulmonary disease.[J].2010,29(12).