title: Cortisol plays a role in the high environmental ammonia associated suppression of the immune response in zebrafish.
abstract: Exposure to high environmental ammonia (HEA) levels increases the vulnerability of fishes to parasitic, viral and bacterial diseases. We tested the hypothesis that elevated plasma cortisol levels play a role in the HEA-mediated immunosuppression in fishes. To this end, we tested the effect of exogenous cortisol treatment on the lipopolysaccharide (LPS)-induced immune response in zebrafish (Danio rerio). Also, to test whether glucocorticoid receptor (GR) signaling is involved in HEA-mediated immunosuppression, zebrafish were treated with mifepristone, a GR antagonist, and the LPS-induced immune response assessed after HEA exposure. We evaluated a panel of important immunity-related genes including interleukin 1β (il1b) and suppressor of cytokine signaling (socs-1a, 2, 3) and acute phase response genes [serum amyloid A (saa), transferrin (tfa), leukocyte cell-derived chemotaxin 2-like (lect2l), haptoglobin (hp), hepcidin (=hepatic anti-microbial peptide hamp), and complement component 3b (c3b)] by real-time quantitative PCR. Our results demonstrate that exogenous cortisol administration as well as elevated cortisol levels in response to HEA exposure modulate mRNA transcript levels of key mediators of the innate immune response in zebrafish. Mifepristone treatment reduced whole body cortisol levels and eliminated the HEA-mediated changes in transcript abundance of socs1a, il1b, as well as APR genes. Together, these results suggest that the HEA effect on the innate immune response is in part mediated by cortisol signaling, while the mode of action, including the receptors involved remains to be elucidated.
authors.affiliation: Centro Interdisciplinar de Investigação Marinha e Ambiental, Porto, Portugal; Instituto de Ciências Biomédicas Abel Salazar, Porto, Portugal.
authors.forename: A F
authors.initials: AF
authors.lastname: Gonçalves
authors.affiliation: Instituto de Biologia Molecular e Celular, Porto, Portugal.
authors.forename: J V
authors.initials: JV
authors.lastname: Neves
authors.affiliation: Centro Interdisciplinar de Investigação Marinha e Ambiental, Porto, Portugal; Instituto de Ciências Biomédicas Abel Salazar, Porto, Portugal.
authors.forename: J
authors.initials: J
authors.lastname: Coimbra
authors.affiliation: Instituto de Biologia Molecular e Celular, Porto, Portugal; Instituto de Ciências Biomédicas Abel Salazar, Porto, Portugal.
authors.forename: P
authors.initials: P
authors.lastname: Rodrigues
authors.affiliation: Department of Biology, University of Waterloo, Waterloo, Canada.
authors.forename: M M
authors.initials: MM
authors.lastname: Vijayan
authors.affiliation: Centro Interdisciplinar de Investigação Marinha e Ambiental, Porto, Portugal. Electronic address: jmwilson@wlu.ca.
authors.forename: J M
authors.initials: JM
authors.lastname: Wilson
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D000531:Altitude; D000641:Ammonia / Q000009:adverse effects*; D000818:Animals; D004777:Environment; D005786:Gene Expression Regulation / Q000187:drug effects; D006854:Hydrocortisone / Q000378:metabolism*; D007109:Immunity / Q000187:drug effects / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics / Q000276:immunology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000209:Acute-Phase Proteins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D029961:Zebrafish Proteins; D000641:Ammonia; D006854:Hydrocortisone
keywords: Acute phase response; Cortisol; Innate immunity; Mifepristone; Zebrafish