title: Maternal Disononyl Phthalate Exposure Activates Allergic Airway Inflammation via Stimulating the Phosphoinositide 3-kinase/Akt Pathway in Rat Pups.
abstract: OBJECTIVE
  To evaluate the effect of diisononyl phthalate (DINP) exposure during gestation and lacta- tion on allergic response in pups and to explore the role of phosphoinositide 3-kinase/Akt pathway on it.
  
  
  METHODS
  Female Wistar rats were treated with DINP at different dosages (0, 5, 50, and 500 mg/kg of body weight per day). The pups were sensitized and challenged by ovalbumin (OVA). The airway response was assessed; the airway histological studies were performed by hematoxylin and eosin (HE) staining; and the relative cytokines in phosphoinositide 3-kinase (PI3K)/Akt pathway were measured by enzyme-linked immunosorbent assay (ELISA) and western blot analysis.
  
  
  RESULTS
  There was no significant difference in DINP's effect on airway hyperresponsiveness (AHR) between male pups and female pups. In the 50 mg/(kg·d) DINP-treated group, airway response to OVA significantly increased and pups showed dramatically enhanced pulmonary resistance (RI) compared with those from controls (P<0.05). Enhanced Akt phosphorylation and NF-κB translocation, and Th2 cytokines expression were observed in pups of 50 mg/(kg·d) DINP-treated group. However, in the 5 and 500 mg/(kg·d) DINP-treated pups, no significant effects were observed.
  
  
  CONCLUSIONS
  There was an adjuvant effect of DINP on allergic airway inflammation in pups. Maternal DINP exposure could promote OVA-induced allergic airway response in pups in part by upregulation of PI3K/Akt pathway.
authors: Minhang District Center for Disease Control and Prevention, Shanghai 201101, China; Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China.
authors: Li
authors: L
authors: Chen
authors: Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China.
authors: Jiao
authors: J
authors: Chen
authors: Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China.
authors: Chang Ming
authors: CM
authors: Xie
authors: Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China.
authors: Yan
authors: Y
authors: Zhao
authors: Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China.
authors: Xiu
authors: X
authors: Wang
authors: Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China.
authors: Yun Hui
authors: YH
authors: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001991:Bronchitis / Q000139:chemically induced*; D001992:Bronchoalveolar Lavage Fluid; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006967:Hypersensitivity / Q000209:etiology*; D008297:Male; D018811:Maternal Exposure; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D010795:Phthalic Acids / Q000633:toxicity*; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D010795:Phthalic Acids; C032279:phthalic acid; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Allergic airway inflammation; Asthma; DINP; Maternal exposure; PI3K/Akt