Journal
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
Volume 307, Issue 6, Pages L471-L481Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00324.2013
Keywords
bronchial epithelium; lung; substance P; neurokinin; NK-1R
Categories
Funding
- NIH Program Project Grant Pulmonary Effects of Environmental Oxidant Pollutants [NIEHS ES000628]
- NIH National Center for Research Resources Grant [NCRR RR000169]
- National Institutes of Health (NIH)
- NIH Roadmap for Medical Research
- United States Environmental Protection Agency (EPA) [FP917122]
- US EPA
- EPA [FP917122, 672934] Funding Source: Federal RePORTER
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Children are uniquely susceptible to ozone because airway and lung growth continue for an extensive period after birth. Early-life exposure of the rhesus monkey to repeated ozone cycles results in region-specific disrupted airway/lung growth, but the mediators and mechanisms are poorly understood. Substance P (SP), neurokinin-1 receptor (NK-1R); and nuclear receptor Nur77 (NR4A1) are signaling pathway components involved in ozone-induced cell death. We hypothesize that acute ozone (AO) exposure during postnatal airway development disrupts SP/NK-1R/Nur77 pathway expression and that these changes correlate with increased ozone-induced cell death. Our objectives were to 1) spatially define the normal development of the SP/NK-1R/Nur77 pathway in conducting airways; 2) compare how postnatal age modulates responses to AO exposure; and 3) determine how concomitant, episodic ozone exposure modifies age-specific acute responses. Male infant rhesus monkeys were assigned at age 1 mo to two age groups, 2 or 6 mo, and then to one of three exposure subgroups: filtered air (FA), FA+AO (AO: 8 h/day x 2 days), or episodic biweekly ozone exposure cycles (EAO: 8 h/day x 5 days/14-day cycle+AO). O-3 = 0.5 ppm. We found that 1) ozone increases SP/NK-1R/Nur77 pathway expression in conducting airways, 2) an ozone exposure cycle (5 days/cycle) delivered early at age 2 mo resulted in an airway that was hypersensitive to AO exposure at the end of 2 mo, and 3) continued episodic exposure (11 cycles) resulted in an airway that was hyposensitive to AO exposure at 6 mo. These observations collectively associate with greater overall inflammation and epithelial cell death, particularly in early postnatal (2 mo), distal airways.
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