Plasticizer, di(2-ethylhexyl)phthalate (DEHP) enhances cockroach allergen extract-driven airway inflammation by enhancing pulmonary Th2 as well as Th17 immune responses in mice

Journal Article · Sun Jul 15 04:00:00 EDT 2018 · Environmental Research

DOI:https://doi.org/10.1016/J.ENVRES.2018.02.039· OSTI ID:23105780

Alfardan, Ali S.; Nadeem, Ahmed; Ahmad, Sheikh F.; Al-Harbi, Naif O.; Al-Harbi, Mohammad M.; AlSharari, Shakir D. ^[1]

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1. Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, PO Box 2455, Riyadh 11451 (Saudi Arabia)

Highlights: • DEHP enhances CE-induced airway inflammation/mucus secretion in mice. • DEHP enhances expression of costimulatory molecules on dendritic cells. • DEHP enhances expression of pro-inflammatory cytokines in dendritic cells. • DEHP down regulates expression of E-cadherin in airway epithelial cells. In recent decades, there has been a gradual increase in the prevalence of asthma. Various factors including environmental pollutants have contributed to this phenomenon. Plasticizer, di(2-ethylhexyl)phthalate (DEHP) is one of the commonest environmental pollutants due to its association with plastic products. DEHP gets released from plastic products easily leading to respiratory exposure in humans. As a consequence, DEHP is associated with allergic asthma in humans and animals. DEHP is reported to act as an adjuvant in ovalbumin-induced mouse models of asthma at high doses. However, these studies mostly looked into the role of DEHP on Th2 cytokines/eosinophilic inflammation without investigating the role of airway epithelial cells (AECs)/dendritic cells (DCs)/Th17 cells. Its adjuvant activity with natural allergens such as cockroach allergens at tolerable daily intake needs to be explored. Cockroach allergens and DEHP may be inhaled together due to their coexistence in work place as well as household environments. Therefore, effect of DEHP was assessed in cockroach allergens extract (CE)-induced mouse model of asthma. Airway inflammation, histopathology, mucus secretion, and immune responses related to Th2/Th17/DCs and AECs were assessed in mice with DEHP exposure alone and in combination with CE. Our study shows that DEHP converts CE-induced eosinophilic inflammation into mixed granulocytic inflammation by promoting Th2 as well as Th17 immune responses. This was probably due to downregulation of E-cadherin in AECs, and enhancement of costimulatory molecules (MHCII/CD86/CD40)/pro-inflammatory cytokines (IL-6/MCP-1) in DCs by DEHP. This suggests that DEHP facilitates development of mixed granulocytic airway inflammation in the presence of a natural allergen.

• OSTI ID: 23105780
• Journal Information: Environmental Research, Journal Name: Environmental Research Vol. 164; ISSN ENVRAL; ISSN 0013-9351
• Country of Publication: United States
• Language: English

Related Subjects

54 ENVIRONMENTAL SCIENCES
ASTHMA
DENDRITES
HOUSEHOLDS
HUMAN POPULATIONS
INFLAMMATION
INTAKE
LYMPHOKINES
MICE
MOLECULES
OVALBUMIN
PHTHALATES
PLASTICIZERS
PLASTICS
POLLUTANTS
SECRETION