title: Maternal Antiasthma Simplified Herbal Medicine Intervention therapy prevents airway inflammation and modulates pulmonary innate immune responses in young offspring mice.
abstract: BACKGROUND
  Maternal asthma is a risk factor for asthma in offspring; however, transmission of the risk for allergic asthma without direct offspring sensitization has not been explored.
  
  
  OBJECTIVE
  To determine whether offspring from mothers with ovalbumin (OVA)-sensitized asthma would develop airway disease at first-ever exposure to OVA and whether preconception maternal treatment with the Antiasthma Simplified Herbal Medicine Intervention (ASHMI) or dexamethasone (DEX) could modify this risk in offspring.
  
  
  METHODS
  Female BALB/c mice (F0) with OVA-induced asthma were generated using established protocols. Mice with asthma were treated with ASHMI, DEX, or water for 6 to 7 weeks. Naive mice served as controls. Subsequently, mice were mated. Twelve-day-old F1 offspring received 3 consecutive intranasal low- or high-dose OVA exposures without sensitization. Forty-eight hours later, airway inflammation, mucus hypersecretion, serum antibodies, and cytokines were evaluated.
  
  
  RESULTS
  Offspring from OVA-sensitized mothers, but not naive mothers, showed eosinophilic and neutrophilic airway inflammation, and mucus hyperplasia after OVA exposure and he presence of OVA-specific IgG1 and IgG2a. Offspring of ASHMI- and DEX-treated mothers showed decreased airway inflammation and mucus hypersecretion after low-dose OVA (P < .05-.001 for the 2 comparisons vs offspring of OVA/Sham mothers). Offspring of ASHMI-treated, but not DEX-treated, mothers were protected after the high-dose OVA challenge (P < .05-.01 vs offspring OVA/Sham). Maternal ASHMI therapy was associated with increased IgG2a (P < .01 vs offspring of OVA/Sham mothers) and decreased bronchoalveolar lavage fluid CXCL-1 and eotaxin-1 levels (P < .01 and P < .05, respectively, vs offspring of OVA/Sham mothers).
  
  
  CONCLUSIONS
  Offspring of mothers with OVA-induced asthma developed airway inflammation and mucus to first-ever OVA exposure without prior sensitization. Maternal therapy with ASHMI was superior to DEX in decreasing offspring susceptibility to airway disease and could be a strategy to lower asthma prevalence.
authors.affiliation: Department of Pediatrics, Mount Sinai School of Medicine, New York, New York; Department of Bioactivity and Food Analysis, Institute in Food Science Research (CIAL), CSIC-UAM, Madrid, Spain.
authors.forename: Iván
authors.initials: I
authors.lastname: López-Expósito
authors.affiliation: Department of Pediatrics, Mount Sinai School of Medicine, New York, New York. Electronic address: kamal.srivastava@mssm.edu.
authors.forename: Kamal D
authors.initials: KD
authors.lastname: Srivastava
authors.affiliation: Department of Pediatrics, Mount Sinai School of Medicine, New York, New York.
authors.forename: Neil
authors.initials: N
authors.lastname: Birmingham
authors.affiliation: Department of Pediatrics, Mount Sinai School of Medicine, New York, New York.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Castillo
authors.affiliation: Division of Pulmonary, Allergy, Critical Care Medicine, Department of Medicine; Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, Columbia University, New York, New York.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Miller
authors.affiliation: Department of Pediatrics, Mount Sinai School of Medicine, New York, New York.
authors.forename: Xiu-Min
authors.initials: XM
authors.lastname: Li
mesh_terms: D000818:Animals; D005260:Female; D008297:Male; D051379:Mice; D011247:Pregnancy; D000906:Antibodies / Q000097:blood; D001249:Asthma / Q000276:immunology / Q000628:therapy; D054413:Chemokine CCL11 / Q000235:genetics / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D003907:Dexamethasone / Q000008:administration & dosage; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage; D007113:Immunity, Innate / Q000187:drug effects; D007112:Immunity, Maternally-Acquired / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000276:immunology; D018811:Maternal Exposure / Q000009:adverse effects; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000517:prevention & control
chemical_list: D000906:Antibodies; C555782:ASHMI herbal formula; D054413:Chemokine CCL11; D054360:Chemokine CXCL1; D016207:Cytokines; D003907:Dexamethasone; D004365:Drugs, Chinese Herbal