Adrenergic and glucocorticoid modulation of the sterile inflammatory response

Cox, Stewart S.; Speaker, Kristin J.; Beninson, Lida A.; Craig, W.; Paton, Madeline M.; Fleshner, Monika

doi:10.1016/j.bbi.2013.11.018

Cited by 30 publications

(31 citation statements)

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“…Since down-regulation of miR-142-5p is known to enable cytokine-mediated survival [27], prazosin administration should decrease associated inflammatory cytokine activity. Indeed, previous research demonstrates that pre-treatment with prazosin prior to tail shock stress attenuates stress-induced elevations in monocyte chemotactic protein-1 (MCP-1) and IL-1β [51]. In line with these findings, administration of phenylephrine, an α 1 -ADR agonist, in the absence of stress induces an elevation of plasma Hsp72 similar to levels seen in rats exposed to inescapable tail shock [35]; however, additional studies are needed to determine if stimulation of the α 1 -ADR in the absence of an acute stressor modifies exosomal Hsp72 and miRNAs.…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, α 1 -ADR activation may be critical for Hsp72 synthesis or miRNA transcription. A recent study demonstrated that blockade of the α 1 -ADR in stressed rats attenuated stress-induced increases of intracellular Hsp72 in the spleen, liver, and subcutaneous adipose [51], however, it is unknown if these are the tissue source for plasma exosome Hsp72. Future studies should elucidate the tissue origin of these stress modified exosomes and examine if α 1 -ADR blockade in stressed animals affects their cytosolic Hsp72 and miR-142-5p, thus indicating whether α 1 -ADR activation is critical for their transcription and synthesis or their exosomal loading.…”

Section: Discussionmentioning

confidence: 99%

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Acute Stressor Exposure Modifies Plasma Exosome-Associated Heat Shock Protein 72 (Hsp72) and microRNA (miR-142-5p and miR-203)

et al. 2014

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Exosomes, biologically active nanoparticles (40–100 nm) released by hematopoietic and non-hematopoietic cells, contain a variety of proteins and small, non-coding RNA known as microRNA (miRNA). Exposure to various pathogens and disease states modifies the composition and function of exosomes, but there are no studies examining in vivo exosomal changes evoked by the acute stress response. The present study reveals that exposing male Fisher 344 rats to an acute stressor modulates the protein and miRNA profile of circulating plasma exosomes, specifically increasing surface heat shock protein 72 (Hsp72) and decreasing miR-142-5p and -203. The selected miRNAs and Hsp72 are associated with immunomodulatory functions and are likely a critical component of stress-evoked modulation of immunity. Further, we demonstrate that some of these stress-induced modifications in plasma exosomes are mediated by sympathetic nervous system (SNS) activation of alpha-1 adrenergic receptors (ADRs), since drug-mediated blockade of the receptors significantly attenuates the stress-induced modifications of exosomal Hsp72 and miR-142-5p. Together, these findings demonstrate that activation of the acute stress response modifies the proteomic and miRNA profile of exosomes released into the circulation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Acute Stressor Exposure Modifies Plasma Exosome-Associated Heat Shock Protein 72 (Hsp72) and microRNA (miR-142-5p and miR-203)

et al. 2014

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“…Blood concentrations of several DAMPs (i.e., Hsp72, uric acid) can be increased in rats after exposure to a predatory cat with no physical contact [33], or predatory ferret odor [34], or uncontrollable 1.5mA, 5-s shocks delivered across the tail (i.e., tailshock) [12, 13, 20]. Increases in blood concentrations of Hsp72 after tailshock is blocked by alpha-adrenergic, but not beta-or glucocorticoid-, receptor antagonists [35–37]}. Alpha-adrenergic receptors bind catecholamines released after SNS activation from nerve terminals (norepinephrine) and adrenal medullary cells (epinephrine).…”

Section: Stimulation Of Stress-induced Sterile Inflammation: Dampsmentioning

confidence: 99%

“…Furthermore, exosomes purified from hypertensive rats stimulated the up-regulation of ICAM-1 in endothelial cells [74]; and exosomes purified from chronic heart failure patients increased inflammatory signaling in endothelial cells [75]. Given that stress-induced modulation of exosomal DAMPs (i.e., Hps72), miRNA (i.e., 142-5p) and inflammatory proteins were blocked by an alpha adrenergic-receptor antagonist [14, 35–37], it is possible that high levels of catecholamines due to stressor exposure or pathology, increase pro-inflammatory signals delivered to tissues via exosomes.…”

Section: Regulation Of Stress-induced Sterile Inflammation: Mirna Andmentioning

confidence: 99%

Exosomes, DAMPs and miRNA: Features of Stress Physiology and Immune Homeostasis

Fleshner

Crane

2017

Trends in Immunology

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Psychological/physical stressors and local tissue damage increase inflammatory proteins in tissues and blood in humans and animals, in the absence of pathogenic disease. Stress-evoked cytokine/chemokine responses or “sterile inflammation”, can facilitate host survival and/or negatively impact health, depending on context. Recent evidence supports the hypothesis that systemic stress-evoked sterile inflammation is initiated by the sympathetic nervous system, resulting in the elevation of exosome-associated immune-stimulatory endogenous danger/damage associated molecular patterns (DAMPs) and a reduction in immune-inhibitory microRNA (miRNA) which are carried in the circulation to tissues throughout the body. We propose that sterile inflammation should be considered an elemental feature of the stress response and that circulating exosomes transporting immune- modulatory signals, may play a role fundamental role in immune homeostasis.

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“…While obesity contributes to the development of disease through the chronic expression of proinflammatory cytokines [3], recent work from our laboratory demonstrates that proinflammatory cytokine expression also occurs in the WAT of normal weight rats which is mediated, in part, by the acute stress response [4, 5]. Rats exposed to 100 acute tail shocks, for example, demonstrate a 10-fold increase in the expression of interleukin- (IL-) 1 β in the subcutaneous WAT compartment that does not occur in intraperitoneal (epididymal + retroperitoneal depots) or visceral (omental + mesenteric depots) WAT [4].…”

Section: Introductionmentioning

confidence: 99%

A Single Bout of Fasting (24 h) Reduces Basal Cytokine Expression and Minimally Impacts the Sterile Inflammatory Response in the White Adipose Tissue of Normal Weight F344 Rats

Speaker

Paton

Cox

et al. 2016

Mediators of Inflammation

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Sterile inflammation occurs when inflammatory proteins are increased in blood and tissues by nonpathogenic states and is a double-edged sword depending on its cause (stress, injury, or disease), duration (transient versus chronic), and inflammatory milieu. Short-term fasting can exert a host of health benefits through unknown mechanisms. The following experiment tested if a 24 h fast would modulate basal and stress-evoked sterile inflammation in plasma and adipose. Adult male F344 rats were either randomized to ad libitum access to food or fasted for 24 h prior to 0 (control), 10, or 100, 1.5 mA-5 s intermittent, inescapable tail shocks (IS). Glucose, nonesterified free fatty acids (NEFAs), insulin, leptin, and corticosterone were measured in plasma and tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, IL-6, and IL-10 in plasma, and subcutaneous, intraperitoneal, and visceral compartments of white adipose tissue (WAT). In control rats, a 24 h fast reduced all measured basal cytokines in plasma and visceral WAT, IL-1β and IL-6 in subcutaneous WAT, and IL-6 in intraperitoneal WAT. In stressed rats (IS), fasting reduced visceral WAT TNF-α, subcutaneous WAT IL-1β, and plasma insulin and leptin. Short-term fasting may thus prove to be a useful dietary strategy for reducing peripheral inflammatory states associated with visceral obesity and chronic stress.

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Adrenergic and glucocorticoid modulation of the sterile inflammatory response

Cited by 30 publications

References 50 publications

Acute Stressor Exposure Modifies Plasma Exosome-Associated Heat Shock Protein 72 (Hsp72) and microRNA (miR-142-5p and miR-203)

Acute Stressor Exposure Modifies Plasma Exosome-Associated Heat Shock Protein 72 (Hsp72) and microRNA (miR-142-5p and miR-203)

Exosomes, DAMPs and miRNA: Features of Stress Physiology and Immune Homeostasis

A Single Bout of Fasting (24 h) Reduces Basal Cytokine Expression and Minimally Impacts the Sterile Inflammatory Response in the White Adipose Tissue of Normal Weight F344 Rats

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