title: Transcriptional analysis of LPS-stimulated activation of trout (Oncorhynchus mykiss) monocyte/macrophage cells in primary culture treated with cortisol.
abstract: Primary immune responses to pathogen invasion are mediated by the innate immune system in which tissue macrophages play a key role. During infectious processes glucocorticoids generally may function to dampen inflammatory responses. In this study, the ability of cortisol to directly modulate the transcriptional response of rainbow trout macrophages to the cellular activator lipopolysaccharide (LPS) was investigated. The results indicate that cortisol significantly inhibits the well-described LPS-dependent induction of the expression of TNF-alpha2, a pro-inflammatory cytokine. In order to further characterize the molecular effects of LPS and the immunomodulatory role of cortisol, the in vitro macrophage response to LPS in the absence or presence of 12-h cortisol exposure was analyzed utilizing a salmonid-specific microarray platform. Genes that were stimulated or inhibited with LPS plus cortisol fell into several major functional groups. The first, a general "response" group comprising genes within ontology classes including the response to external stimuli, stress, humoral immunity and apoptosis, exhibited a significant increase after LPS stimulation, whereas suppression of this response was observed in the presence of cortisol. LPS stimulated other genes in a second group involved in cell signalling and also genes in a third group involved in the activation of transcription. Categories activated with cortisol were mainly related to various aspects of metabolism (including protein biosynthesis, binding and transport of ions) and structural proteins (mainly cytoskeleton and microtubules). The immunomodulatory action of cortisol on LPS-stimulated macrophages therefore appears more complex than simply the antagonism of LPS-induced transcriptional responses.
authors.affiliation: Unitat de Fisiologia Animal, Departament de Biologia Cel.lular, Fisiologia i d'Immunologia, Facultat de Ciencies, Universitat Autonoma de Barcelona, Bellaterra, Barcelona, Spain. Simon.MacKenzie@uab.es
authors.forename: S
authors.initials: S
authors.lastname: MacKenzie
authors.forename: D
authors.initials: D
authors.lastname: Iliev
authors.forename: C
authors.initials: C
authors.lastname: Liarte
authors.forename: H
authors.initials: H
authors.lastname: Koskinen
authors.forename: J V
authors.initials: JV
authors.lastname: Planas
authors.forename: F W
authors.initials: FW
authors.lastname: Goetz
authors.forename: H
authors.initials: H
authors.lastname: Mölsä
authors.forename: A
authors.initials: A
authors.lastname: Krasnov
authors.forename: L
authors.initials: L
authors.lastname: Tort
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006854:Hydrocortisone / Q000494:pharmacology; D007155:Immunologic Factors / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D017686:Oncorhynchus mykiss / Q000276:immunology*; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D007155:Immunologic Factors; D008070:Lipopolysaccharides; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D006854:Hydrocortisone