Role of interleukin-6 signaling pathway in adverse health effects induced by air pollution

SHAO Wenpu; PENG Renzhen; XU Yanyi

doi:10.11836/JEOM22344

Volume 40 Issue 3

Apr. 2023

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Journal of Environmental and Occupational Medicine > 2023 > 40(3): 355-361. > DOI: 10.11836/JEOM22344

SHAO Wenpu, PENG Renzhen, XU Yanyi. Role of interleukin-6 signaling pathway in adverse health effects induced by air pollution[J]. Journal of Environmental and Occupational Medicine, 2023, 40(3): 355-361. DOI: 10.11836/JEOM22344

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Role of interleukin-6 signaling pathway in adverse health effects induced by air pollution

Department of Environmental Health, School of Public Health, Fudan University, Shanghai, 200032, China

Funds: This study was funded.

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Corresponding author:
XU Yanyi, E-mail: yanyi_xu@fudan.edu.cn
Received Date: August 14, 2022
Accepted Date: January 11, 2023
Available Online: April 05, 2023

Graphical Abstract

Abstract

Abstract

Air pollution is one of the most important environmental issues in China and worldwide, as well as a critical public health problem affecting human health. With the implementation of emission reduction and other programs, the air quality in China has been improved dramatically in recent years, but is still worse than the WHO guideline recommended levels. Numerous epidemiological and toxicological studies have shown that short-term or long-term exposure to air pollution is strongly associated with respiratory diseases, cardiovascular diseases, diabetes, and so forth, in which interleukin-6 (IL-6), a well-known inflammatory factor, may play an important role. Studies have found that IL-6 can bind to interleukin-6 receptor (IL-6R) , which leads to the recruiting and activation of glycoprotein 130, and then the formed IL-6/IL-6R/gp130 complex triggers the janus kinase/signal transducer and activator of transcription, Src homology-2 domain-containing protein tyrosine phosphatase-2/mitogen-activated protein kinase, and phosphatidylinositol 3-kinase/protein kinase B signaling pathways. All of these signaling pathways are found to be involved in a variety of physiopathological processes. In the present review, information about the IL-6 signaling pathway and its role in air pollution-induced adverse health effects was systematically reviewed, hoping to provide insights for the future prevention and control policies.
- air pollution,
- interleukin-6,
- signaling pathway,
- respiratory system,
- toxicological effect,
- molecular mechanism

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References

[1]	ZHANG S, MWIBERI S, PICKFORD R, et al. Longitudinal associations between ambient air pollution and insulin sensitivity: results from the KORA cohort study[J]. Lancet Planet Health, 2021, 5(1): e39-e49. doi: 10.1016/S2542-5196(20)30275-8
[2]	YIN P, BRAUER M, COHEN A J, et al. The effect of air pollution on deaths, disease burden, and life expectancy across China and its provinces, 1990-2017: an analysis for the Global Burden of Disease Study 2017[J]. Lancet Planet Health, 2020, 4(9): e386-e398. doi: 10.1016/S2542-5196(20)30161-3
[3]	WANG M, AARON C P, MADRIGANO J, et al. Association between long-term exposure to ambient air pollution and change in quantitatively assessed emphysema and lung function[J]. JAMA, 2019, 322(6): 546-556. doi: 10.1001/jama.2019.10255
[4]	LIANG L, CAI Y, BARRATT B, et al. Associations between daily air quality and hospitalisations for acute exacerbation of chronic obstructive pulmonary disease in Beijing, 2013-17: an ecological analysis[J]. Lancet Planet Health, 2019, 3(6): e270-e279. doi: 10.1016/S2542-5196(19)30085-3
[5]	HANSEN A B, RAVNSKJÆR L, LOFT S, et al. Long-term exposure to fine particulate matter and incidence of diabetes in the Danish Nurse Cohort[J]. Environ Int, 2016, 91: 243-250. doi: 10.1016/j.envint.2016.02.036
[6]	POPE III C A, TURNER M C, BURNETT R T, et al. Relationships between fine particulate air pollution, cardiometabolic disorders, and cardiovascular mortality[J]. Circ Res, 2015, 116(1): 108-115. doi: 10.1161/CIRCRESAHA.116.305060
[7]	FURMAN D, CAMPISI J, VERDIN E, et al. Chronic inflammation in the etiology of disease across the life span[J]. Nat Med, 2019, 25(12): 1822-1832. doi: 10.1038/s41591-019-0675-0
[8]	SHOU Y, HUANG Y, ZHU X, et al. A review of the possible associations between ambient PM_2.5 exposures and the development of Alzheimer's disease[J]. Ecotoxicol Environ Saf, 2019, 174: 344-352. doi: 10.1016/j.ecoenv.2019.02.086
[9]	LIBBY P. Inflammation during the life cycle of the atherosclerotic plaque[J]. Cardiovasc Res, 2021, 117(13): 2525-2536.
[10]	ZHANG J J, WEI Y, FANG Z. Ozone pollution: a major health hazard worldwide[J]. Front Immunol, 2019, 10: 2518. doi: 10.3389/fimmu.2019.02518
[11]	LEE J J, KIM J H, SONG D S, et al. Effect of short- to long-term exposure to ambient particulate matter on cognitive function in a cohort of middle-aged and older adults: KoGES[J]. Int J Environ Res Public Health, 2022, 19(16): 9913. doi: 10.3390/ijerph19169913
[12]	FONKEN L K, XU X, WEIL Z M, et al. Air pollution impairs cognition, provokes depressive-like behaviors and alters hippocampal cytokine expression and morphology[J]. Mol Psychiatry, 2011, 16(10): 987-995. doi: 10.1038/mp.2011.76
[13]	WANG Y, LI C, ZHANG X, et al. Exposure to PM_2.5 aggravates Parkinson's disease via inhibition of autophagy and mitophagy pathway[J]. Toxicology, 2021, 456: 152770. doi: 10.1016/j.tox.2021.152770
[14]	SAHU B, MACKOS A R, FLODEN A M, et al. Particulate matter exposure exacerbates amyloid-β plaque deposition and gliosis in APP/PS1 mice[J]. J Alzheimer’s Dis, 2021, 80(2): 761-774. doi: 10.3233/JAD-200919
[15]	GU Y, HAO S, LIU K, et al. Airborne fine particulate matter (PM_2.5) damages the inner blood-retinal barrier by inducing inflammation and ferroptosis in retinal vascular endothelial cells[J]. Sci Total Environ, 2022, 838(Pt 4): 156563.
[16]	YANG M, JALAVA P, HAKKARAINEN H, et al. Fine and ultrafine airborne PM influence inflammation response of young adults and toxicological responses in vitro[J]. Sci Total Environ, 2022, 836: 155618. doi: 10.1016/j.scitotenv.2022.155618
[17]	FAN Z, PUN V C, CHEN X C, et al. Personal exposure to fine particles (PM_2.5) and respiratory inflammation of common residents in Hong Kong[J]. Environ Res, 2018, 164: 24-31. doi: 10.1016/j.envres.2018.02.009
[18]	CHUNG K F, TOGBE D, RYFFEL B. Editorial: ozone as a driver of lung inflammation and innate immunity and as a model for lung disease[J]. Front Immunol, 2021, 12: 714161. doi: 10.3389/fimmu.2021.714161
[19]	SHOU Y, ZHU X, ZHU D, et al. Ambient PM_2.5 chronic exposure leads to cognitive decline in mice: from pulmonary to neuronal inflammation[J]. Toxicol Lett, 2020, 331: 208-217. doi: 10.1016/j.toxlet.2020.06.014
[20]	CAMPOS-RODRIGUEZ F, CORDERO-GUEVARA J, ASENSIO-CRUZ M I, et al. Interleukin 6 as a marker of depression in women with sleep apnea[J]. J Sleep Res, 2021, 30(1): e13035.
[21]	PIETERS M, FERREIRA M, DE MAAT M P M, et al. Biomarker association with cardiovascular disease and mortality -The role of fibrinogen. A report from the NHANES study[J]. Thromb Res, 2021, 198: 182-189. doi: 10.1016/j.thromres.2020.12.009
[22]	CHASE K A, CONE J J, ROSEN C, et al. The value of interleukin 6 as a peripheral diagnostic marker in schizophrenia[J]. BMC Psychiatry, 2016, 16: 152. doi: 10.1186/s12888-016-0866-x
[23]	CHALLA F, SEIFU D, SILESHI M, et al. Serum level of high sensitive C-reactive protein and IL - 6 markers in patients with treatment-resistant schizophrenia in Ethiopia: a comparative study[J]. BMC Psychiatry, 2021, 21(1): 428. doi: 10.1186/s12888-021-03443-4
[24]	GEORGAKIS M K, MALIK R, RICHARDSON T G, et al. Associations of genetically predicted IL-6 signaling with cardiovascular disease risk across population subgroups[J]. BMC Med, 2022, 20(1): 245. doi: 10.1186/s12916-022-02446-6
[25]	ZHU H, WU Y, KUANG X, et al. Effect of PM_2.5 exposure on circulating fibrinogen and IL-6 levels: a systematic review and meta-analysis[J]. Chemosphere, 2021, 271: 129565. doi: 10.1016/j.chemosphere.2021.129565
[26]	TANG H, CHENG Z, LI N, et al. The short- and long-term associations of particulate matter with inflammation and blood coagulation markers: a meta-analysis[J]. Environ Pollut, 2020, 267: 115630. doi: 10.1016/j.envpol.2020.115630
[27]	MURAKAMI M, KAMIMURA D, HIRANO T. Pleiotropy and specificity: insights from the interleukin 6 family of cytokines[J]. Immunity, 2019, 50(4): 812-831. doi: 10.1016/j.immuni.2019.03.027
[28]	UCIECHOWSKI P, DEMPKE W C M. Interleukin-6: a Masterplayer in the cytokine network[J]. Oncology, 2020, 98(3): 131-137. doi: 10.1159/000505099
[29]	KAUR S, BANSAL Y, KUMAR R, et al. A panoramic review of IL-6: structure, pathophysiological roles and inhibitors[J]. Bioorg Med Chem, 2020, 28(5): 115327. doi: 10.1016/j.bmc.2020.115327
[30]	SCHUMACHER N, SCHMIDT S, SCHWARZ J, et al. Circulating soluble IL-6R but not ADAM17 activation drives mononuclear cell migration in tissue inflammation[J]. J Immunol, 2016, 197(9): 3705-3715. doi: 10.4049/jimmunol.1600909
[31]	HEPPLER L N, FRANK D A. Targeting oncogenic transcription factors: therapeutic implications of endogenous STAT inhibitors[J]. Trends Cancer, 2017, 3(12): 816-827. doi: 10.1016/j.trecan.2017.10.004
[32]	ROSE-JOHN S. Local and systemic effects of interleukin-6 (IL-6) in inflammation and cancer[J]. FEBS Lett, 2022, 596(5): 557-566. doi: 10.1002/1873-3468.14220
[33]	TANAKA T, NARAZAKI M, KISHIMOTO T. Interleukin (IL-6) immunotherapy[J]. Cold Spring Harb Perspect Biol, 2018, 10(8): a028456. doi: 10.1101/cshperspect.a028456
[34]	AKBARI M, HASSAN-ZADEH V. IL-6 signalling pathways and the development of type 2 diabetes[J]. Inflammopharmacology, 2018, 26(3): 685-698. doi: 10.1007/s10787-018-0458-0
[35]	LEE S M, KIM C E, PARK H Y, et al. Aryl hydrocarbon receptor-targeted therapy for CD4⁺ T cell-mediated idiopathic pneumonia syndrome in mice[J]. Blood, 2022, 139(22): 3325-3339. doi: 10.1182/blood.2021013849
[36]	SCHRAUFNAGEL D E, BALMES J R, COWL C T, et al. Air Pollution and Noncommunicable diseases: a review by the forum of international respiratory societies' environmental committee, Part 2: air pollution and organ systems[J]. Chest, 2019, 155(2): 417-426. doi: 10.1016/j.chest.2018.10.041
[37]	BO Y C, CHANG L Y, GUO C, et al. Reduced ambient PM_2.5, better lung function, and decreased risk of chronic obstructive pulmonary disease[J]. Environ Int, 2021, 156: 106706. doi: 10.1016/j.envint.2021.106706
[38]	SUN X W, LIN Y N, DING Y J, et al. Surfaxin attenuates PM_2.5-induced airway inflammation via restoring surfactant proteins in rats exposed to cigarette smoke[J]. Environ Res, 2022, 203: 111864. doi: 10.1016/j.envres.2021.111864
[39]	YANG B, GUO J, XIAO C. Effect of PM_2.5 environmental pollution on rat lung[J]. Environ Sci Pollut Res Int, 2018, 25(36): 36136-36146. doi: 10.1007/s11356-018-3492-y
[40]	ALFARO-MORENO E, TORRES V, MIRANDA J, et al. Induction of IL-6 and inhibition of IL-8 secretion in the human airway cell line Calu-3 by urban particulate matter collected with a modified method of PM sampling[J]. Environ Res, 2009, 109(5): 528-535. doi: 10.1016/j.envres.2009.02.010
[41]	FENG S, GAO D, LIAO F, et al. The health effects of ambient PM_2.5 and potential mechanisms[J]. Ecotoxicol Environ Saf, 2016, 128: 67-74. doi: 10.1016/j.ecoenv.2016.01.030
[42]	SONG L, LI D, LI X, et al. Exposure to PM_2.5 induces aberrant activation of NF-κB in human airway epithelial cells by downregulating miR-331 expression[J]. Environ Toxicol Pharmacol, 2017, 50: 192-199. doi: 10.1016/j.etap.2017.02.011
[43]	BUDINGER G R S, MCKELL J L, URICH D, et al. Particulate matter-induced lung inflammation increases systemic levels of PAI-1 and activates coagulation through distinct mechanisms[J]. PLoS One, 2011, 6(4): e18525. doi: 10.1371/journal.pone.0018525
[44]	LIU C W, LEE T L, CHEN Y C, et al. PM_2.5-induced oxidative stress increases intercellular adhesion molecule-1 expression in lung epithelial cells through the IL-6/AKT/STAT3/NF-κB-dependent pathway[J]. Part Fibre Toxicol, 2018, 15(1): 4. doi: 10.1186/s12989-018-0240-x
[45]	CHEN M, ZHOU H, XU Y, et al. From the cover: lung-specific overexpression of constitutively active IKK2 induces pulmonary and systemic inflammations but not hypothalamic inflammation and glucose intolerance[J]. Toxicol Sci, 2017, 160(1): 4-14. doi: 10.1093/toxsci/kfx154
[46]	THOMPSON A M S, ZANOBETTI A, SILVERMAN F, et al. Baseline repeated measures from controlled human exposure studies: associations between ambient air pollution exposure and the systemic inflammatory biomarkers IL-6 and fibrinogen[J]. Environ Health Perspect, 2010, 118(1): 120-124. doi: 10.1289/ehp.0900550
[47]	VO T T T, HSU C Y, WEE Y, et al. Carbon monoxide-releasing molecule-2 ameliorates particulate matter-induced aorta inflammation via toll-like receptor/NADPH oxidase/ROS/NF-κB/IL-6 inhibition[J]. Oxid Med Cell Longev, 2021, 2021: 2855042.
[48]	MUTLU G M, GREEN D, BELLMEYER A, et al. Ambient particulate matter accelerates coagulation via an IL-6-dependent pathway[J]. J Clin Invest, 2007, 117(10): 2952-2961. doi: 10.1172/JCI30639
[49]	LONG M H, ZHANG C, XU D Q, et al. PM_2.5 aggravates diabetes via the systemically activated IL-6-mediated STAT3/SOCS3 pathway in rats' liver[J]. Environ Pollut, 2020, 256: 113342. doi: 10.1016/j.envpol.2019.113342
[50]	LIN C H, WAN C, LIU W S, et al. PM_2.5 induces early epithelial mesenchymal transition in human proximal tubular epithelial cells through activation of IL-6/STAT3 pathway[J]. Int J Mol Sci, 2021, 22(23): 12734. doi: 10.3390/ijms222312734
[51]	BRUCKER N, MORO A M, CHARÃO M F, et al. Biomarkers of occupational exposure to air pollution, inflammation and oxidative damage in taxi drivers[J]. Sci Total Environ, 2013, 463-464: 884-893. doi: 10.1016/j.scitotenv.2013.06.098
[52]	DADVAND P, NIEUWENHUIJSEN M J, AGUSTI A, et al. Air pollution and biomarkers of systemic inflammation and tissue repair in COPD patients[J]. Eur Respir J, 2014, 44(3): 603-613. doi: 10.1183/09031936.00168813
[53]	JOHNSTON R A, SCHWARTZMAN I N, FLYNT L, et al. Role of interleukin-6 in murine airway responses to ozone[J]. Am J Physiol Lung Cell Mol Physiol, 2005, 288(2): L390-L397. doi: 10.1152/ajplung.00007.2004
[54]	KASAHARA D I, KIM H Y, MATHEWS J A, et al. Pivotal role of IL-6 in the hyperinflammatory responses to subacute ozone in adiponectin-deficient mice[J]. Am J Physiol Lung Cell Mol Physiol, 2014, 306(6): L508-L520. doi: 10.1152/ajplung.00235.2013

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