This study aims to investigate the role of Toll-like receptors (TLRs) on fine particulate matter (PM2.5)-induced inflammatory responses of vascular endothelial cells. Inflammatory factors and TLRs were examined in the aorta of mice after nonsurgical intratracheal instillation of PM2.5 as well as in the human umbilical vein endothelial cells (HUVECs) treated with PM2.5. In addition, the effects of TLR2 and TLR4 inhibitors in the secretion of interleukin 6 (IL-6) and IL-1β and the expression of TLRs were determined in the HUVECs. The results showed that PM2.5 could increase the expression of IL-1β, IL-6, TLR2, and TLR4 in vitro and in vivo. Anti-TLR2 IgG or TAK242, an inhibitor of TLR4, decreased the secretion of IL-1β and IL-6 by HUVECs and reduced the expression of corresponding TLRs. In conclusion, we demonstrate that both TLR2 and TLR4 are involved in PM2.5-induced inflammatory responses of vascular endothelial cells. Inhibition of TLR2 and TLR4 expression has the potential to prevent PM2.5-induced cardiovascular diseases.
BaiRZhangLLiuY, et al. (2010) Pulmonary responses to printer toner particles in mice after intratracheal instillation. Toxicology Letters199(3): 288–300.
2.
BrookRDRajagopalanSPopeCA3rd, et al. (2010) Particulate matter air pollution and cardiovascular disease: an update to the scientific statement from the American Heart Association. Circulation121(21): 2331–2378.
3.
BurnettRTSmith-DoironMStiebD, et al. (1999) Effects of particulate and gaseous air pollution on cardiorespiratory hospitalizations. Archives of Environmental Health: An International Journal54(2): 130–139.
4.
ChenYLiHLiM, et al. (2017) Salvia miltiorrhiza polysaccharide activates T lymphocytes of cancer patients through activation of TLRs mediated-MAPK and NF-κB signaling pathways. Journal of Ethnopharmacology200: 165–173.
5.
ChukkapalliSSVelskoIMRivera-KwehMF, et al. (2017) Global TLR2 and 4 deficiency in mice impacts bone resorption, inflammatory markers and atherosclerosis to polymicrobial infection. Molecular Oral Microbiology32(3): 211–225.
6.
DongLSunWLiF, et al. (2019) The harmful effects of acute PM2.5 exposure to the heart and a novel preventive and therapeutic function of CEOs. Scientific Reports9(1): 3495.
7.
EdfeldtKSwedenborgJHanssonGK, et al. (2002) Expression of toll-like receptors in human atherosclerotic lesions: a possible pathway for plaque activation. Circulation105(10): 1158–1161.
8.
FernandoIPSJayawardenaTUKimHS, et al. (2019) Beijing urban particulate matter-induced injury and inflammation in human lung epithelial cells and the protective effects of fucosterol from Sargassum binderi (Sonder ex J. Agardh). Environmental Research172: 150–158.
9.
GayNJSymmonsMFGangloffM, et al. (2014) Assembly and localization of toll-like receptor signalling complexes. Nature Reviews Immunology14(8): 546–558.
10.
GBD 2013 Mortality and Causes of Death Collaborators (2015) Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet385(9963): 117–171.
11.
GuHFLiNXuZQ, et al. (2019) Chronic unpredictable mild stress promotes atherosclerosis via HMGB1/TLR4-mediated downregulation of PPARγ/LXRα/ABCA1 in ApoE-/- Mice. Frontiers in Physiology10: 165.
12.
HaoZLZhangZJLuDZ, et al. (2019) Organophosphorus flame retardants impair intracellular lipid metabolic function in human hepatocellular cells. Chemical Research in Toxicology32(6): 1250–1258.
13.
HartzAMBauerBBlockML, et al. (2008) Diesel exhaust particles induce oxidative stress, proinflammatory signaling, and P-glycoprotein up-regulation at the blood-brain barrier. Faseb Journal Official Publication of the Federation of American Societies for Experimental Biology22(8): 2723–2733.
14.
JinYWuZWangN, et al. (2016) Association of EGF receptor and NLRs signaling with cardiac inflammation and fibrosis in mice exposed to fine particulate matter. Journal of Biochemical and Molecular Toxicology30(9): 429–437.
15.
LuCChangCHPalmerC, et al. (2018) Neonicotinoid residues in fruits and vegetables: an integrated dietary exposure assessment approach. Environmental Science and Technology52(5): 3175–3184.
16.
MichelsenKSWongMHShahPK, et al. (2004) Lack of toll like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E. Proc Natl Acad Sci U S A101(29): 10679–10684.
17.
Montiel-DávalosAIbarra-Sánchez MdeJVentura-GallegosJL, et al. (2010) Oxidative stress and apoptosis are induced in human endothelial cells exposed to urban particulate matter. Toxicology in Vitro24(1): 135–141.
18.
MullickAETobiasPSCurtissLK (2005) Modulation of atherosclerosis in mice by toll-like receptor 2. Journal of Clinical Investigation115(11): 3149–3156.
19.
NoreenMArshadM (2015) Association of TLR1, TLR2, TLR4, TLR6, and TIRAP polymorphisms with disease susceptibility. Immunologic Research62(2): 234–252.
20.
PopeCA3rdBhatnagarAMcCrackenJP, et al. (2000) Exposure to fine particulate air pollution is associated with endothelial injury and systemic inflammation. Circulation Research119(11): 1204–1214.
21.
PopeCA3rdBurnettRTThurstonGD, et al. (2004) Cardiovascular mortality and long-term exposure to particulate air pollution: epidemiological evidence of general pathophysiological pathways of disease. Circulation109(1): 71–77.
22.
PoursafaPKelishadiR (2010) Air pollution, platelet activation and atherosclerosis. Inflammation and Allergy Drug Targets9(5): 387–392.
23.
RattanapinyopitukKShimadaAMoritaT, et al. (2013) Ultrastructural changes in the air-blood barrier in mice after intratracheal instillations of Asian sand dust and gold nanoparticles. Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft fur Toxikologische Pathologie65(7-8): 1043–1051.
24.
RehoJJRahmouniK (2017) Oxidative and inflammatory signals in obesity-associated vascular abnormalities. Clinical Science131(14): 1689–1700.
25.
RoshanMHTamboAPaceNP (2016) The role of TLR2, TLR4, and TLR9 in the pathogenesis of atherosclerosis. International Journal of Inflammation2016: 1532832.
26.
RundellKWHoffmanJRCavistonR, et al. (2007) Inhalation of ultrafine and fine particulate matter disrupts systemic vascular function. Inhalation Toxicology19(2): 133–l40.
27.
SatohTAkiraS (2016) Toll-like receptor signaling and its inducible proteins. Microbiology Spectrum4(6). DOI: 10.1128/microbiolspec.MCHD-0040-2016.
28.
ShiJDengHZhangM (2017) Curcumin pretreatment protects against PM2.5-induced oxidized low-density lipoprotein-mediated oxidative stress and inflammation in human microvascular endothelial cells. Molecular Medicine Reports16(3): 2588–2594.
29.
ShoenfeltJMitkusRJZeislerR, et al. (2009) Involvement of TLR2 and TLR4 in inflammatory immune responses induced by fine and coarse ambient air particulate matter. Journal of Leukocyte Biology86(2): 303–312.
30.
WangCYangJHaoZ, et al. (2017) Suppression of progesterone synthesis in human trophoblast cells by fine particulate matter primarily derived from industry. Environmental Pollution231(Pt 1): 1172–1180.
31.
WangCYueSHaoZ, et al. (2019) Pubertal exposure to the endocrine disruptor mono-2-ethylhexyl ester at body burden level caused cholesterol imbalance in mice. Environmental Pollution244: 657–666.
32.
WangHShenXTianG, et al. (2019) AMPKα2 deficiency exacerbates long-term PM2.5 exposure-induced lung injury and cardiac dysfunction. Free Radical Biology and Medicine121: 202–214.
33.
WangJSTsengCYChaoMW (2017) Diesel exhaust particles contribute to endothelia apoptosis via autophagy pathway. Toxicological Sciences156(1): 72–83.
34.
XiaWRFuWWangQ, et al. (2017) Autophagy induced FHL2 upregulation promotes IL-6 production by activating the NF-κB pathway in mouse aortic endothelial cells after exposure to PM2.5. International Journal of Molecular Sciences18(7): 1484.
35.
YueWTongLLiuX, et al. (2018) Short term PM2.5 exposure caused a robust lung inflammation, vascular remodeling, and exacerbated transition from left ventricular failure to right ventricular hypertrophy. Redox Biology22: 101161.
36.
ZhangQLuZChangCH, et al. (2019) Dietary risk of neonicotinoid insecticides through fruit and vegetable consumption in school-age children. Environment International126: 672–681.
37.
ZhaoCLiaoJChuW, et al. (2012) Involvement of TLR2 and TLR4 and Th1/Th2 shift in inflammatory responses induced by fine ambient particulate matter in mice. Inhalation Toxicology24(13): 918–927.
38.
ZhuJZhuLYangJ, et al. (2018) Proteomic analysis of human umbilical vein endothelial cells exposed to PM2.5*. Journal of Zhejiang University-Science B19(6): 458–470.
