Early Life Ozone Exposure Results in Dysregulated Innate Immune Function and Altered microRNA Expression in Airway Epithelium
Air Pollution and Epigenetics
Journal of Environmental Protection
2013; 4 (8A)
The Innate Immune Response to LPS in Airway Epithelium is Dependent Upon Chronological Age and Antecedent Exposures.
American journal of respiratory cell and molecular biology
Postnatal episodic ozone results in persistent attenuation of pulmonary and peripheral blood responses to LPS challenge
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
2011; 300 (3): L462-L471
The immune mechanisms for neonatal susceptibility to respiratory pathogens are poorly understood. Given that mucosal surfaces serve as a first line of host defense, we hypothesized that the innate immune response to infectious agents may be developmentally regulated in airway epithelium. To test this hypothesis, we determined if expression of IL-8 and IL-6 in airway epithelium following lipopolysaccharide (LPS) exposure is dependent upon chronological age. Tracheas from infant, juvenile and adult rhesus monkeys were first exposed to LPS ex vivo, then processed for air-liquid interface primary airway epithelial cell cultures and secondary LPS treatment in vitro. As compared with adult cultures, infant and juvenile cultures expressed significantly reduced levels of IL-8 following LPS treatment. IL-8 protein in cultures increased with animal age, whereas LPS-induced IL-6 protein was predominantly associated with juvenile cultures. Toll-like receptor (TLR) pathway RT-PCR arrays showed differential expression of multiple mRNAs in infant cultures relative to adult cultures, including IL-1?, TLR10, and the peptidoglycan recognition protein PGLYRP2. To determine whether the age dependent cytokine response to LPS is reflective of antecedent exposures, we assessed primary airway epithelial cell cultures established from juvenile monkeys housed in filtered air since birth. Filtered air housed animal cultures exhibited LPS-induced IL-8 and IL-6 expression that was discordant with age matched ambient air housed animals; a single LPS aerosol in vivo also affected this cytokine profile. Cumulatively, our findings demonstrate that the innate immune response to LPS in airway epithelium is variable with age and may be modulated by prior environmental exposures.
View details for PubMedID 23600597
Early life is a dynamic period of growth for the lung and immune system. We hypothesized that ambient ozone exposure during postnatal development can affect the innate immune response to other environmental challenges in a persistent fashion. To test this hypothesis, we exposed infant rhesus macaque monkeys to a regimen of 11 ozone cycles between 30 days and 6 mo of age; each cycle consisted of ozone for 5 days (0.5 parts per million at 8 h/day) followed by 9 days of filtered air. Animals were subsequently housed in filtered air conditions and challenged with a single dose of inhaled LPS at 1 yr of age. After completion of the ozone exposure regimen at 6 mo of age, total peripheral blood leukocyte and polymorphonuclear leukocyte (PMN) numbers were reduced, whereas eosinophil counts increased. In lavage, total cell numbers at 6 mo were not affected by ozone, however, there was a significant reduction in lymphocytes and increased eosinophils. Following an additional 6 mo of filtered air housing, only monocytes were increased in blood and lavage in previously exposed animals. In response to LPS challenge, animals with a prior history of ozone showed an attenuated peripheral blood and lavage PMN response compared with controls. In vitro stimulation of peripheral blood mononuclear cells with LPS resulted in reduced secretion of IL-6 and IL-8 protein in association with prior ozone exposure. Collectively, our findings suggest that ozone exposure during infancy can result in a persistent effect on both pulmonary and systemic innate immune responses later in life.
View details for DOI 10.1152/ajplung.00254.2010
View details for Web of Science ID 000287915100016
View details for PubMedID 21131396