Prenatal stress enhances susceptibility of murine adult offspring toward airway inflammation

TY - JOUR

T1 - Prenatal stress enhances susceptibility of murine adult offspring toward airway inflammation

AU - Pincus-Knackstedt, Maike K

AU - Joachim, Ricarda A

AU - Blois, Sandra M

AU - Douglas, Alison J

AU - Orsal, Arif S

AU - Klapp, Burghard F

AU - Wahn, Ulrich

AU - Hamelmann, Eckard

AU - Arck, Petra C

PY - 2006/12/15

Y1 - 2006/12/15

N2 - Allergic asthma is one of the most prevalent and continuously increasing diseases in developed countries. Its clinical features include airway hyperresponsiveness and inflammation upon allergen contact. Furthermore, an emerging area of research subsumed as fetal programming evaluates the impact of environmental insults in utero on the incidence of diseases in later life. The aim of this study was to identify whether prenatal exposure to stress, which constitutes a severe environmental insult, perpetuates airway inflammation in later life. Our experiments were performed in mice and revealed that prenatally stressed adult offspring indeed show an increased vulnerability toward airway hyperresponsiveness and inflammation. Furthermore, we provide persuasive insights on dysregulated pathways of the cellular and humoral immune response upon Ag challenge in prenatally stressed adult offspring, reflected by a Th2 greater Th1 adaptive immune response and increased CCR3 and IgE levels in vivo. Additionally, APCs derived from prenatally stressed offspring trigger clonal expansion of Th2 cells in vitro. We also deliver experimental evidence for a reduced corticotrophin-releasing hormone expression in the paraventricular nucleus of adult offspring in response to prenatal stress. Furthermore, behavioral analyses indicate an increase in anxiety in these mice. In conclusion, our data will facilitate future research aiming to identify the individual impact, hierarchy, and redundancy of multiple key protagonists in airway inflammation in an interdisciplinary context. This will foster the substantiation of disease-prevention strategies, such as asthma, during the prenatal period.

AB - Allergic asthma is one of the most prevalent and continuously increasing diseases in developed countries. Its clinical features include airway hyperresponsiveness and inflammation upon allergen contact. Furthermore, an emerging area of research subsumed as fetal programming evaluates the impact of environmental insults in utero on the incidence of diseases in later life. The aim of this study was to identify whether prenatal exposure to stress, which constitutes a severe environmental insult, perpetuates airway inflammation in later life. Our experiments were performed in mice and revealed that prenatally stressed adult offspring indeed show an increased vulnerability toward airway hyperresponsiveness and inflammation. Furthermore, we provide persuasive insights on dysregulated pathways of the cellular and humoral immune response upon Ag challenge in prenatally stressed adult offspring, reflected by a Th2 greater Th1 adaptive immune response and increased CCR3 and IgE levels in vivo. Additionally, APCs derived from prenatally stressed offspring trigger clonal expansion of Th2 cells in vitro. We also deliver experimental evidence for a reduced corticotrophin-releasing hormone expression in the paraventricular nucleus of adult offspring in response to prenatal stress. Furthermore, behavioral analyses indicate an increase in anxiety in these mice. In conclusion, our data will facilitate future research aiming to identify the individual impact, hierarchy, and redundancy of multiple key protagonists in airway inflammation in an interdisciplinary context. This will foster the substantiation of disease-prevention strategies, such as asthma, during the prenatal period.

KW - Animals

KW - Anxiety/etiology

KW - Asthma/etiology

KW - Disease Susceptibility

KW - Female

KW - Hypersensitivity/etiology

KW - Immunity

KW - Inflammation/etiology

KW - Male

KW - Mice

KW - Mice, Inbred BALB C

KW - Pregnancy

KW - Prenatal Exposure Delayed Effects/immunology

KW - Respiratory System/pathology

KW - Stress, Physiological/complications

KW - Th1 Cells/immunology

KW - Th2 Cells/immunology

U2 - 10.4049/jimmunol.177.12.8484

DO - 10.4049/jimmunol.177.12.8484

M3 - SCORING: Journal article

C2 - 17142746

VL - 177

SP - 8484

EP - 8492

JO - J IMMUNOL

JF - J IMMUNOL

SN - 0022-1767

IS - 12

ER -