Inhalation of environmental stressors & chronic inflammation: Autoimmunity and neurodegeneration

Abstract

Human life expectancy and welfare has decreased because of the increase in environmental stressors in the air. An environmental stressor is a natural or human-made component present in our environment that upon reaching an organic system produces a coordinated response. This response usually involves a modification of the metabolism and physiology of the system. Inhaled environmental stressors damage the airways and lung parenchyma, producing irritation, recruitment of inflammatory cells, and oxidative modification of biomolecules. Oxidatively modified biomolecules, their degradation products, and adducts with other biomolecules can reach the systemic circulation, and when found in higher concentrations than normal they are considered to be biomarkers of systemic oxidative stress and inflammation. We classify them as metabolic stressors because they are not inert compounds; indeed, they amplify the inflammatory response by inducing inflammation in the lung and other organs. Thus the lung is not only the target for environmental stressors, but it is also the source of a number of metabolic stressors that can induce and worsen preexisting chronic inflammation. Metabolic stressors produced in the lung have a number of effects in tissues other than the lung, such as the brain, and they can also abrogate the mechanisms of immunotolerance. In this review, we discuss recent published evidence that suggests that inflammation in the lung is an important connection between air pollution and chronic inflammatory diseases such as autoimmunity and neurodegeneration, and we highlight the critical role of metabolic stressors produced in the lung. The understanding of this relationship between inhaled environmental pollutants and systemic inflammation will help us to: 1) understand the molecular mechanism of environment-associated diseases, and 2) find new biomarkers that will help us prevent the exposure of susceptible individuals and/or design novel therapies.

The immune effects of naturally occurring and synthetic nanoparticles

“…Activation of JNK was also noted at lower exposure concentrations of ultrafine particles [73]. The systemic inflammation resulting from exposure to ultrafine particles produces oxidative stress that may also play a role in neurodegeneration [74].…”

Airborne particulate matter selectively activates endoplasmic reticulum stress response in the lung and liver tissues

“…PM 2.5 , primarily derived from stationary and traffic-related combustion sources, has been linked strongly with cardiovascular disease and metabolic disease (6,10,12,35,47). Recent studies have addressed the impacts of airborne PM 2.5 on the functioning of signaling pathways with significant roles in redox homeostasis and inflammation (14,48,49,54). However, the understanding of molecular and cellular mechanisms underlying PM 2.5 -associated systemic diseases remains incomplete.…”

Human health hazards of persistent inorganic and carbon nanoparticles

“…Deposition may occur in the cardiovascular system, liver, brain, testis, spleen, stomach, and kidney [1-3, 15, 34-38 Apart from the effects of nanoparticles translocated from the respiratory system, negative effects of inhaled nanoparticles may also be associated with metabolic stressors and platelet-leukocyte aggregates which originate in inflammatory lung disease [43][44][45]. Metabolic stressors include inflammatory cytokines and oxidized biomolecules [43]. These stressors may trigger chronic inflammation in organs, and may lead to cardiovascular disease [43].…”

“…Metabolic stressors include inflammatory cytokines and oxidized biomolecules [43]. These stressors may trigger chronic inflammation in organs, and may lead to cardiovascular disease [43]. Also there is the possibility that metabolic stressors negatively affect development of the fetus [45].…”