Explore the vast range of titles available.

Regular interactions between commensal bacteria and the enteric mucosal immune environment are necessary for normal immunity. Alterations of the commensal bacterial communities or mucosal barrier can disrupt immune function. Chronic stress interferes with bacterial community structure (specifically, α-diversity) and the integrity of the intestinal barrier. These interferences can contribute to chronic stress-induced increases in systemic IL-6 and TNF-α. Chronic stress, however, produces many physiological changes that could indirectly influence immune activity. In addition to IL-6 and TNF-α, exposure to acute stressors upregulates a plethora of inflammatory proteins, each having unique synthesis and release mechanisms. We therefore tested the hypothesis that acute stress-induced inflammatory protein responses are dependent on the commensal bacteria, and more specifically, lipopolysaccharide (LPS) shed from Gram-negative intestinal commensal bacteria. We present evidence that both reducing commensal bacteria using antibiotics and neutralizing LPS using endotoxin inhibitor (EI) attenuates increases in some (inflammasome dependent, IL-1 and IL-18), but not all (inflammasome independent, IL-6, IL-10, and MCP-1) inflammatory proteins in the blood of male F344 rats exposed to an acute tail shock stressor. Acute stress did not impact α- or β- diversity measured using 16S rRNA diversity analyses, but selectively reduced the relative abundance of Prevotella. These findings indicate that commensal bacteria contribute to acute stress-induced inflammatory protein responses, and support the presence of LPS-mediated signaling in stress-evoked cytokine and chemokine production. The selectivity of the commensal bacteria in stress-evoked IL-1β and IL-18 responses may implicate the inflammasome in this response.

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.

(2012) Commensal Bacteria and MAMPs Are Necessary for Stress-Induced Increases in IL-1β and IL-18 but Not IL-6, IL-10 or MCP-1. (2013) Correction: Commensal Bacteria and MAMPs Are Necessary for Stress-Induced Increases in IL-1β and IL-18 but Not IL-6, IL-10 or MCP-1.

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.

Regular interactions between commensal bacteria and the enteric mucosal immune environment are necessary for normal immunity. Alterations of the commensal bacterial communities or mucosal barrier can disrupt immune function. Chronic stress interferes with bacterial community structure (specifically, [alpha]-diversity) and the integrity of the intestinal barrier. These interferences can contribute to chronic stress-induced increases in systemic IL-6 and TNF-[alpha]. Chronic stress, however, produces many physiological changes that could indirectly influence immune activity. In addition to IL-6 and TNF-[alpha], exposure to acute stressors upregulates a plethora of inflammatory proteins, each having unique synthesis and release mechanisms. We therefore tested the hypothesis that acute stress-induced inflammatory protein responses are dependent on the commensal bacteria, and more specifically, lipopolysaccharide (LPS) shed from Gram-negative intestinal commensal bacteria. We present evidence that both reducing commensal bacteria using antibiotics and neutralizing LPS using endotoxin inhibitor (EI) attenuates increases in some (inflammasome dependent, IL-1 and IL-18), but not all (inflammasome independent, IL-6, IL-10, and MCP-1) inflammatory proteins in the blood of male F344 rats exposed to an acute tail shock stressor. Acute stress did not impact [alpha]- or [beta]- diversity measured using 16S rRNA diversity analyses, but selectively reduced the relative abundance of Prevotella. These findings indicate that commensal bacteria contribute to acute stress-induced inflammatory protein responses, and support the presence of LPS-mediated signaling in stress-evoked cytokine and chemokine production. The selectivity of the commensal bacteria in stress-evoked IL-1[beta] and IL-18 responses may implicate the inflammasome in this response.

The relationship between an organism and its surroundings involves the evaluation of environmental input and subsequent activation of appropriate responses. When the environment is perturbed, an organism will undergo a series of changes collectively referred to as the “stress response”. Acute activation of the stress response modulates many physiological systems. One way these systems are modulated is via the release of “alarm signals”. Within the context of the immune system, these alarm signals are referred to as danger associated molecular patterns (DAMPs). DAMPs are endogenous molecules capable of binding a diverse set of receptors and initiating or enhancing a variety of immune responses. One such DAMP, extracellular heat shock protein 72 (eHsp72), is released into the circulation following exposure to a variety of physiological stressors. Intracellular Hsp72 is found in most cells of the body, and is similarly increased within these cells following stressor exposure. eHsp72, however, appears to originate from a limited subset of tissues. The identity of the specific tissue that releases Hsp72 has not been determined. Based upon data from previous examinations of Hsp72 release, it was hypothesized that the small intestine releases Hsp72 as part of the stress response. Using a model of intense acute stress (50, 5s, 1.5mA inescapable tailshocks) the release of Hsp72 can be induced. Through the subsequent manipulation of small intestinal synthesis of Hsp72, release of Hsp72, and variability of the eHsp72 response, the role of the small intestine in the release of Hsp72 was investigated. Increasing synthesis of Hsp72 in the small intestine resulted in an increase of eHsp72 in the circulation. Blocking release of Hsp72 resulted in an increase, or build-up of Hsp72 within the small intestine. Finally, increasing variability within the eHsp72 response revealed a predictive relationship between Hsp72 in the small intestine and eHsp72 in the circulation. A statistical combination of these results supports the hypothesis that the small intestine releases Hsp72 as part of the stress response.

Systemic sterile inflammatory responses (SSIRs) are characterized by an increase in concentrations of blood and tissue cytokines, chemokines and other inflammatory proteins. SSIRs are commonly evoked by trauma or exposure to severe stressors and may result in negative consequences including multi-organ failure and death. Current attempts to treat SSIRs are often ineffective, reflecting the need for additional characterization of the signals and pathways that drive these processes. Specifically, it is important to explore recent advances in our understanding of the underlying signaling pathways and inflammatory proteins involved in SSIRs such as those that follow stressor exposure. The goals of this dissertation, therefore, are the following: (1) characterize the network of diverse cytokines, chemokines, inflammatory proteins and their receptors involved in SSIRs; (2) discuss factors impacted by the stress response including danger- and microbe associated molecular patterns (DAMPs and MAMPs) that may contribute to signaling processes to stimulate SSIRs; and (3) highlight a recently discovered signaling complex, the inflammasome, and its role in stress-induced SSIRs. We propose that systemic sterile inflammatory processes are initiated by a wide variety of molecules and involve the release of a plethora of cytokines, chemokines, and other immunomodulatory proteins. Importantly, we present evidence that this cytokine storm, although initiated by many diverse signals, may converge on the inflammasome. Additional research is necessary to determine whether the inflammasome is a suitable pharmacological target for SSIRs.

A summary is presented of the Surface Heat Budget of the Arctic Ocean (SHEBA) project, with a focus on the field experiment that was conducted from October 1997 to October 1998. The primary objective of the field work was to collectocean, ice, and atmospheric datasets over a full annual cycle that could be used to understand the processes controlling surface heat exchanges—in particular, the ice-albedo feedback and cloud-radiation feedback. This information is being used to improve formulations of arctic ice-ocean-atmosphere processes in climate models and thereby improve simulations of present and future arctic climate. The experiment was deployed from an ice breaker that was frozen into the ice packand allowed to drift for the duration of the experiment. This research platform allowed the use of an extensive suite of instruments that directly measured ocean, atmosphere, and ice properties from both the ship and the ice pack in the immediate vicinity of the ship. This summary describes the project goals, experimental design, instrumentation, and the resulting datasets. Examples of various data products available from the SHEBA project are presented.