MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively regulate gene expression. Within the intestinal epithelium, miRNAs play a critical role in gut homeostasis, and aberrant miRNA expression has been implicated in various disorders associated with intestinal inflammation and barrier disruption. In this study, we sought to profile changes in intestinal epithelial cell miRNA expression after alcohol and burn injury and elucidate their impact on inflammation and barrier integrity.
View Article and Find Full Text PDFOn October 26th, 2022 the annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held as a satellite symposium at the annual meeting of the Society for Leukocyte Biology in Hawaii. The 2022 meeting focused broadly on the immunological consequences of acute, chronic, and prenatal alcohol exposure and how these contribute to damage in multiple organs and tissues. These included alcohol-induced neuroinflammation, impaired lung immunity, intestinal dysfunction, and decreased anti-microbial and anti-viral responses.
View Article and Find Full Text PDFBackground: Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in the United States, with an annual cost of 60 billion dollars. There is evidence suggesting that in the post-TBI period, the gastrointestinal tract plays a central role in driving organ and immune dysfunction and may be the source of increased circulating proinflammatory mediators. In this study, we examined systemic inflammation and bacterial dysbiosis in patients who sustained a TBI with or without polytrauma.
View Article and Find Full Text PDFAlcohol Clin Exp Res (Hoboken)
January 2023
Alcohol intoxication combined with burn injury can lead to life-threatening complications, including sepsis, multiple organ failure, and death. After an acute burn, the gastrointestinal system becomes hypoxic because of fluid loss and reduction of intestinal blood flow. This can cause perturbations in the intestinal epithelial barrier, immune function, and the composition of the gut microbiome.
View Article and Find Full Text PDFUlcerative colitis (UC) is characterized by cycles of active disease flare and inactive disease remission. During UC remission, IL-22 is up-regulated, acting as a hallmark of entrance into UC remission. Recently, we found that in our mouse model of binge alcohol and dextran sodium sulfate (DSS)-induced colitis, alcohol increases severity of UC pathology.
View Article and Find Full Text PDFAlcohol
September 2022
On November 19th, 2021, the annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at Loyola University Chicago Health Sciences Campus in Maywood, Illinois. The 2021 meeting focused on how alcohol misuse is linked to immune system derangements, leading to tissue and organ damage, and how this research can be translated into improving treatment of alcohol-related disease. This meeting was divided into three plenary sessions: the first session focused on how alcohol misuse affects different parts of the immune system, the second session presented research on mechanisms of organ damage from alcohol misuse, and the final session highlighted research on potential therapeutic targets for treating alcohol-mediated tissue damage.
View Article and Find Full Text PDFOur previous studies have shown that ethanol intoxication combined with burn injury increases intestinal bacterial growth, disrupts the intestinal barrier, and enhances bacterial translocation. Additionally, studies show that Th17 effector cytokines IL-17 and IL-22, which are dependent on IL-23, play important roles in maintaining intestine mucosal barrier integrity. Recent findings suggest neutrophils are a significant source of IL-17 and IL-22.
View Article and Find Full Text PDFBackground: Cardiometabolic (CM) risk affects approximately 25% of adults globally, and is diagnosed by meeting 3 out of 5 of the following CM risk factors: elevated blood pressure, high triglycerides, elevated blood sugar, low high-density lipoprotein (HDL) level, and abdominal obesity. Adults with CM risk are approximately 22% more likely to have higher mortality rates, and alcohol consumption may be associated with higher CM risk. While previous studies have investigated this potential connection, the majority of them did not include African-origin adults.
View Article and Find Full Text PDFBackground: Inflammatory bowel disease (IBD) is established to drive pathological sequelae in organ systems outside the intestine, including the central nervous system (CNS). Many patients exhibit cognitive deficits, particularly during disease flare. The connection between colonic inflammation and neuroinflammation remains unclear and characterization of the neuroinflammatory phenotype in the brain during colitis is ill-defined.
View Article and Find Full Text PDFGut barrier dysfunction is often implicated in pathology following alcohol intoxication and burn injury. MicroRNAs (miRNAs) are negative regulators of gene expression that play a central role in gut homeostasis, although their role after alcohol and burn injury is poorly understood. We performed an integrated analysis of miRNA and RNA sequencing data to identify a network of interactions within small intestinal epithelial cells (IECs) which could promote gut barrier disruption.
View Article and Find Full Text PDFTraumatic injuries, such as burn, are often complicated by ethanol intoxication at the time of injury. This leads to a myriad of complications and post-burn pathologies exacerbated by aberrant immune responses. Recent findings suggest that immune cell dysfunction in the gastrointestinal system is particularly important in deleterious outcomes associated with burn injuries.
View Article and Find Full Text PDFJ Leukoc Biol
November 2021
The gastrointestinal (GI) tract is a highly dynamic structure essential for digestion, nutrient absorption, and providing an interface to prevent gut bacterial translocation. In order to maintain the barrier function, the gut utilizes many defense mechanisms including proliferation, apoptosis, and apical junctional complexes. Disruption of any of these parameters due to injury or disease could negatively impact the intestinal barrier function and homeostasis resulting in increased intestine inflammation, permeability, bacterial dysbiosis, and tissue damage.
View Article and Find Full Text PDFBurn injuries are a common form of traumatic injury that leads to significant morbidity and mortality worldwide. Burn injuries are characterized by inflammatory processes and alterations in numerous organ systems and functions. Recently, it has become apparent that the gastrointestinal bacterial microbiome is a key component of regulating the immune response and recovery from burn and can also contribute to significant detrimental sequelae after injury, such as sepsis and multiple organ failure.
View Article and Find Full Text PDFAlcohol can potentiate disease in a mouse model of dextran sodium sulfate (DSS) colitis; however, the underlying mechanism remains to be established. In this study, we assessed whether the potentiated disease could be related to and , as changes in their relative abundance can impact intestinal health. We also assessed whether the intestinal barrier is compromised after alcohol and DSS as it may increase bacterial translocation and liver inflammation.
View Article and Find Full Text PDFEthanol remains a confounder in postburn pathology, which is associated with an impaired intestinal barrier. Previously, we demonstrated that ethanol and burn injury reduce intestinal oxygen delivery (hypoxia) and alters microRNA (miR) expression in small intestinal epithelial cells. Hypoxia has been shown to influence expression of miRs and miR biogenesis components.
View Article and Find Full Text PDF6-Formylindolo (3, 2-b) Carbazole (FICZ) is a ligand of aryl hydrocarbon receptor (AHR) which regulates Th17 release of IL-17 and IL-22 production. Earlier, we showed that ethanol combined with burn injury suppresses Th17 responses and disrupts intestinal barrier leading to increased gut bacterial growth and translocation. Since IL-22 is known for its role in intestinal barrier maintenance, we determined whether treatment of mice with FICZ restores T cell IL-22 release and protects intestine barrier following ethanol and burn injury.
View Article and Find Full Text PDFOn November 15, 2019, the 24th annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held as a satellite conference during the annual Society for Leukocyte Biology meeting in Boston, Massachusetts. The 2019 meeting focused on alcohol, immunity, and organ damage, and included two plenary sessions. The first session highlighted new research exploring the mechanisms of alcohol-induced inflammation and liver disease, including effects on lipidomics and lipophagy, regulatory T cells, epigenetics, epithelial cells, and age-related changes in the gut.
View Article and Find Full Text PDFBurn injuries are under-appreciated injuries that are associated with substantial morbidity and mortality. Burn injuries, particularly severe burns, are accompanied by an immune and inflammatory response, metabolic changes and distributive shock that can be challenging to manage and can lead to multiple organ failure. Of great importance is that the injury affects not only the physical health, but also the mental health and quality of life of the patient.
View Article and Find Full Text PDFOn August 27 and 28, 2018, the American Burn Association, in conjunction with Underwriters Laboratories, convened a group of experts on burn and inhalation injury in Washington, DC. The goal of the meeting was to identify and discuss the existing knowledge, data, and modeling gaps related to understanding cutaneous thermal injury and inhalation injury due to exposure from a fire environment, and in addition, address two more areas proposed by the American Burn Association Research Committee that are critical to burn care but may have current translational research gaps (inflammatory response and hypermetabolic response). Representatives from the Underwriters Laboratories Firefighter Safety Research Institute and the Bureau of Alcohol, Tobacco, Firearms and Explosives Fire Research Laboratory presented the state of the science in their fields, highlighting areas that required further investigation and guidance from the burn community.
View Article and Find Full Text PDFInflammasomes are multiprotein complexes that coordinate cellular inflammatory responses and mediate host defense. Following recognition of pathogens and danger signals, inflammasomes assemble and recruit and activate caspase-1, the cysteine protease that cleaves numerous downstream targets, including pro-IL-1β and pro-IL-18 into their biologically active form. In this study, we sought to develop a biosensor that would allow us to monitor the initiation, progression, and resolution of inflammation in living animals.
View Article and Find Full Text PDFPulmonary and systemic insults from inhalation injury can complicate the care of burn patients and contribute to significant morbidity and mortality. However, recent progress in diagnosis and treatment of inhalation injury has not kept pace with the care of cutaneous thermal injury. There are many challenges unique to inhalation injury that have slowed advancement, including deficiencies in our understanding of its pathophysiology, the relative difficulty and subjectivity of bronchoscopic diagnosis, the lack of diagnostic biomarkers, the necessarily urgent manner in which decisions are made about intubation, and the lack of universal recommendations for the application of mucolytics, anticoagulants, bronchodilators, modified ventilator strategies, and other measures.
View Article and Find Full Text PDFOn January 26, 2018, the 23rd annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at the University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado. The meeting consisted of plenary sessions with oral presentations and a poster presentation session. There were four plenary sessions that covered a wide range of topics relating to alcohol use: Alcohol and Liver Disease; Alcohol, Inflammation and Immune Response; Alcohol and Organ Injury; Heath Consequences and Alcohol Drinking.
View Article and Find Full Text PDFMaintenance of the commensal bacteria that comprise the gut microbiome is essential to both gut and systemic health. Traumatic injury, such as burn, elicits a number of changes in the gut, including a shift in the composition of the microbiome (dysbiosis), increased gut leakiness, and bacterial translocation into the lymphatic system and bloodstream. These effects are believed to contribute to devastating secondary complications following burn, including pneumonia, acute respiratory distress syndrome, multi-organ failure, and septic shock.
View Article and Find Full Text PDFOver 1.4 million Americans have been diagnosed with inflammatory bowel disease (IBD), and ulcerative colitis (UC) makes up approximately half of those diagnoses. As a disease, UC cycles between periods of remission and flare, which is characterized by intense abdominal pain, increased weight loss, intestinal inflammation, rectal bleeding, and dehydration.
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