Alcohol-Induced Glycolytic Shift in Alveolar Macrophages Is Mediated by Hypoxia-Inducible Factor-1 Alpha.

Excessive alcohol use increases the risk of developing respiratory infections partially due to impaired alveolar macrophage (AM) phagocytic capacity. Previously, we showed that chronic ethanol (EtOH) exposure led to mitochondrial derangements and diminished oxidative phosphorylation in AM. Since oxidative phosphorylation is needed to meet the energy demands of phagocytosis, EtOH mediated decreases in oxidative phosphorylation likely contribute to impaired AM phagocytosis.

Maintenance of gut barrier integrity after injury: Trust your gut microRNAs.

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.

Alcohol induces mitochondrial derangements in alveolar macrophages by upregulating NADPH oxidase 4.

Excessive alcohol users have increased risk of developing respiratory infections in part due to oxidative stress-induced alveolar macrophage (AM) phagocytic dysfunction. Chronic ethanol exposure increases cellular oxidative stress in AMs via upregulation of NADPH oxidase (Nox) 4, and treatment with the peroxisome proliferator-activated receptor gamma (PPARγ) ligand, rosiglitazone, decreases ethanol-induced Nox4. However, the mechanism by which ethanol induces Nox4 expression and the PPARγ ligand reverses this defect has not been elucidated.

Protective effects of PX478 on gut barrier in a mouse model of ethanol and burn injury.

Ethanol 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.

Summary of the 2019 alcohol and immunology research interest group (AIRIG) meeting: Alcohol-mediated mechanisms of multiple organ injury.

On 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.

Role of HIF-1α in Alcohol-Mediated Multiple Organ Dysfunction.

Excess alcohol consumption is a global crisis contributing to over 3 million alcohol-related deaths per year worldwide and economic costs exceeding $200 billion dollars, which include productivity losses, healthcare, and other effects (e.g., property damages).

Alcohol enhances symptoms and propensity for infection in inflammatory bowel disease patients and a murine model of DSS-induced colitis.

Over 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.

IL-23 restoration of Th17 effector function is independent of IL-6 and TGF-β in a mouse model of alcohol and burn injury.

T cells play a critical role in host defense against intestinal bacteria. We have shown that ethanol combined with burn injury suppresses Peyer's patch (PP) Th17 cytokines 1 d after injury. We assessed the mechanism of suppressed Th17 effector functions.

Interleukin-22 Prevents Microbial Dysbiosis and Promotes Intestinal Barrier Regeneration Following Acute Injury.

Intestine barrier disruption and bacterial translocation can contribute to sepsis and multiple organ failure, leading causes of mortality in burn-injured patients. In addition, findings suggest that ethanol (alcohol) intoxication at the time of injury worsens symptoms associated with burn injury. We have previously shown that interleukin-22 (IL-22) protects from intestinal leakiness and prevents overgrowth of gram-negative bacteria following ethanol and burn injury, but how IL-22 mediates these effects has not been established.

Dysregulation of microRNA biogenesis in the small intestine after ethanol and burn injury.

Ethanol exposure at the time of burn injury is a major contributor to post-burn pathogenesis. Many of the adverse effects associated with ethanol and burn injury are linked to an impaired intestinal barrier. The combined insult causes intestinal inflammation, resulting in tissue damage, altered tight junction expression, and increased intestinal permeability.

Alcohol and inflammatory responses: Highlights of the 2015 Alcohol and Immunology Research Interest Group (AIRIG) meeting.

On September 27, 2015 the 20th 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 Raleigh, NC. The 2015 meeting focused broadly on adverse effects of alcohol and alcohol-use disorders in multiple organ systems. Divided into two plenary sessions, AIRIG opened with the topic of pulmonary inflammation as a result of alcohol consumption, which was followed by alcohol's effect on multiple organs, including the brain and liver.

Effects of Mesalamine Treatment on Gut Barrier Integrity After Burn Injury.

Gut barrier disruption is often implicated in pathogenesis associated with burn and other traumatic injuries. In this study, the authors examined whether therapeutic intervention with mesalamine (5-aminosalicylic acid [5-ASA]), a common anti-inflammatory treatment for patients with inflammatory bowel disease, reduces intestinal inflammation and maintains normal barrier integrity after burn injury. Male C57BL/6 mice were administered an approximately 20% TBSA dorsal scald burn and resuscitated with either 1 ml normal saline or 100 mg/kg of 5-ASA dissolved in saline.

The First Line of Defense: The Effects of Alcohol on Post-Burn Intestinal Barrier, Immune Cells, and Microbiome.

Alcohol (ethanol) is one of the most globally abused substances, and is one of the leading causes of premature death in the world. As a result of its complexity and direct contact with ingested alcohol, the intestine represents the primary source from which alcohol-associated pathologies stem. The gut is the largest reservoir of bacteria in the body, and under healthy conditions, it maintains a barrier preventing bacteria from translocating out of the intestinal lumen.

Summary of the 2014 Alcohol and Immunology Research Interest Group (AIRIG) meeting.

On November 21, 2014 the 19th annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at Loyola University Chicago Health Sciences Campus in Maywood, Illinois. The meeting focused broadly on inflammatory cell signaling responses in the context of alcohol and alcohol-use disorders, and was divided into four plenary sessions focusing on the gut and liver, lung infections, general systemic effects of alcohol, and neuro-inflammation. One common theme among many talks was the differential roles of macrophages following both chronic and acute alcohol intoxication.

The Effects of Alcohol Intoxication and Burn Injury on the Expression of Claudins and Mucins in the Small and Large Intestines.

Alcohol intoxication at the time of burn injury exacerbates postburn pathogenesis. Recent findings suggest gut barrier integrity is compromised after combined alcohol and burn insult, which could contribute to these complications. Tight junction proteins and mucins play critical roles in keeping the gut barrier intact.

Burn Injury Alters the Intestinal Microbiome and Increases Gut Permeability and Bacterial Translocation.

Sepsis remains one of the leading causes of death in burn patients who survive the initial insult of injury. Disruption of the intestinal epithelial barrier has been shown after burn injury; this can lead to the translocation of bacteria or their products (e.g.

Regional variation in expression of pro-inflammatory mediators in the intestine following a combined insult of alcohol and burn injury.

The intestine is segmented into functionally discrete compartments (duodenum, jejunum, ileum, and colon). The present study examined whether alcohol combined with burn injury differently influences cytokine levels in different parts of the intestine. Male mice were gavaged with alcohol (∼2.

Alcohol and inflammatory responses: summary of the 2013 Alcohol and Immunology Research Interest Group (AIRIG) meeting.

Loyola University Chicago, Health Sciences Campus in Maywood, Illinois hosted the 18th annual Alcohol and Immunology Research Interest Group (AIRIG) meeting on November 22, 2013. This year's meeting emphasized alcohol's effect on inflammatory responses in diverse disease states and injury conditions. The meeting consisted of three plenary sessions demonstrating the adverse effects of alcohol, specifically, liver inflammation, adverse systemic effects, and alcohol's role in infection and immunology.