title: Adrenergic and glucocorticoid modulation of the sterile inflammatory response.
abstract: Exposure to an intense, acute stressor, in the absence of a pathogen, alters immune function. Exposure to a single bout of inescapable tail shock increases plasma and tissue concentrations of cytokines, chemokines, and the danger associated molecular pattern (DAMP) Hsp72. Although previous studies have demonstrated that adrenergic receptor (ADR) and glucocorticoid receptor (GCR)-mediated pathways alter pathogen or microbial associated molecular pattern (MAMP)-evoked levels of cytokines, chemokines, and Hsp72, far fewer studies have tested the role of these receptors across multiple inflammatory proteins or tissues to elucidate the differences in magnitude of stress-evoked sterile inflammatory responses. The goals of the current study were to (1) compare the sterile inflammatory response in the circulation, liver, spleen, and subcutaneous (SQ) adipose tissue by measuring cytokine, chemokine, and DAMP (Hsp72) responses; and (2) to test the role of alpha-1 (α1), beta-1 (β1), beta-2 (β2), and beta-3 (β3) ADRs, as well as GCRs in signaling the sterile inflammatory response. The data presented indicate plasma and SQ adipose are significantly more stress responsive than the liver and spleen. Further, administration of ADR and GCR-specific antagonists revealed both similarities and differences in the signaling mechanisms of the sterile inflammatory response in the tissues studied. Finally, given the selective increase in the chemokine monocyte chemotactic protein-1 (MCP-1) in SQ tissue, it may be that SQ adipose is an important site of leukocyte migration, possibly in preparation for infection as a consequence of wounding. The current study helps further our understanding of the tissue-specific differences of the stress-induced sterile inflammatory response.
authors: Department of Integrative Physiology, University of Colorado, Boulder, United States.
authors: Stewart S
authors: SS
authors: Cox
authors: Department of Integrative Physiology, University of Colorado, Boulder, United States.
authors: Kristin J
authors: KJ
authors: Speaker
authors: Department of Integrative Physiology, University of Colorado, Boulder, United States.
authors: Lida A
authors: LA
authors: Beninson
authors: Department of Integrative Physiology, University of Colorado, Boulder, United States.
authors: Wendy C
authors: WC
authors: Craig
authors: Department of Integrative Physiology, University of Colorado, Boulder, United States.
authors: Madeline M
authors: MM
authors: Paton
authors: Department of Integrative Physiology, University of Colorado, Boulder, United States; Center for Neuroscience, University of Colorado, Boulder, United States. Electronic address: fleshner@colorado.edu.
authors: Monika
authors: M
authors: Fleshner
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D004558:Electric Stimulation; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins; D007249:Inflammation / Q000097:blood / Q000378:metabolism*; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011941:Receptors, Adrenergic / Q000502:physiology*; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D013154:Spleen / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D018836:Inflammation Mediators; D011941:Receptors, Adrenergic; D011965:Receptors, Glucocorticoid; C549284:TRAP1 protein, rat
keywords: Acute stress; Catecholamines; Cytokine; Glucocorticoids; Heat shock protein; Monocyte chemotactic protein-1; Sterile inflammation