Possible Mediation by Methylation in Acute Inflammation Following Personal Exposure to Fine Particulate Air Pollution

Abstract

Air pollution may increase cardiovascular and respiratory risk through inflammatory pathways, but evidence for acute effects has been weak and indirect. Between December 2014 and July 2015, we enrolled 36 healthy, nonsmoking college students for a panel study in Shanghai, China, a city with highly variable levels of air pollution. We measured personal exposure to particulate matter with an aerodynamic diameter less than or equal to 2.5 μm (PM 2.5 ) continuously for 72 hours preceding each of 4 clinical visits that included phlebotomy. We measured 4 inflammation proteins and DNA methylation at nearby regulatory cytosine-phosphate-guanine (CpG) loci. We applied linear mixed-effect models to examine associations over various lag times. When results suggested mediation, we evaluated methylation as mediator. Increased PM 2.5 concentration was positively associated with all 4 inflammation proteins and negatively associated with DNA methylation at regulatory loci for tumor necrosis factor alpha (TNF-α) and soluble intercellular adhesion molecule-1. A 10-μg/m 3 increase in average PM 2.5 during the 24 hours preceding blood draw corresponded to a 4.4% increase in TNF-α and a statistically significant decrease in methylation at one of the two studied candidate CpG loci for TNF-α. Epigenetics may play an important role in mediating effects of PM 2.5 on inflammatory pathways. DNA methylation; fine particulate matter; inflammation; mediation analysis; panel study; personal exposure Abbreviations: CI, confidence interval; CpG, cytosine-phosphate-guanine; CVD, cardiovascular disease; PM, particulate matter; PM 2.5 , particulate matter having an aerodynamic diameter less than or equal to 2.5 μm; RD, respiratory disease; sCD40L, soluble cluster of differentiation 40 (CD40) ligand; sICAM-1, soluble intercellular adhesion molecule-1; TNF-α, tumor necrosis factor alpha.

Epigenetic signatures underlying inflammation: an interplay of nutrition, physical activity, metabolic diseases, and environmental factors for personalized nutrition

“…Regarding the effects of air pollution on inflammation by epigenetic modulation, it was reported that the long-term exposure (annual average in the preceding year) to fine particulate matter (PM 2.5 ) was associated with increased TNF-α expression through a reduction in TNF-α gene methylation in women [176]. In addition, changes in TNF methylation were proposed to mediate acute inflammation following personal exposure to fine particulate air pollution [177]. Consistently, adverse cardiac autonomic dysfunctions by PM 2.5 exposure was partially related to methylation changes in the inflammatory TLR2 gene [178].…”

Polyamine Metabolism and Gene Methylation in Conjunction with One-Carbon Metabolism

“…Various types of cellular stress seem to affect epigenetic alterations that may lead to deleterious consequences. Exposure to fine particle air pollution affects DNA methylation status in blood cells [ 178 , 179 , 180 , 181 , 182 , 183 ] and placenta [ 184 ]. Cigarette smoking has adverse effects on health and is associated with changes in epigenetic marks.…”

Temporal cross-correlations between air pollutants and outpatient visits for respiratory and circulatory system diseases in Fuzhou, China

“…For example, NO 2 may cause lung cancer [ 8 ], PM has been associated with increased blood pressure (BP), and a certain concentration of ozone has been associated with decreased BP [ 9 ]. There is an association between PM 2.5 and inflammation [ 10 ]. PM 2.5 can also increase the incidence of various respiratory and circulatory diseases [ 11 , 12 ].…”