CARMA3 Is Critical for the Initiation of Allergic Airway Inflammation.

Innate immune responses to allergens by airway epithelial cells (AECs) help initiate and propagate the adaptive immune response associated with allergic airway inflammation in asthma. Activation of the transcription factor NF-κB in AECs by allergens or secondary mediators via G protein-coupled receptors (GPCRs) is an important component of this multifaceted inflammatory cascade. Members of the caspase recruitment domain family of proteins display tissue-specific expression and help mediate NF-κB activity in response to numerous stimuli. We have previously shown that caspase recruitment domain-containing membrane-associated guanylate kinase protein (CARMA)3 is specifically expressed in AECs and mediates NF-κB activation in these cells in response to stimulation with the GPCR agonist lysophosphatidic acid. In this study, we demonstrate that reduced levels of CARMA3 in normal human bronchial epithelial cells decreases the production of proasthmatic mediators in response to a panel of asthma-relevant GPCR ligands such as lysophosphatidic acid, adenosine triphosphate, and allergens that activate GPCRs such as Alternaria alternata and house dust mite. We then show that genetically modified mice with CARMA3-deficient AECs have reduced airway eosinophilia and proinflammatory cytokine production in a murine model of allergic airway inflammation. Additionally, we demonstrate that these mice have impaired dendritic cell maturation in the lung and that dendritic cells from mice with CARMA3-deficient AECs have impaired Ag processing. In conclusion, we show that AEC CARMA3 helps mediate allergic airway inflammation, and that CARMA3 is a critical signaling molecule bridging the innate and adaptive immune responses in the lung.

Open Gastrostomy of a Gastric Leiomyoma Proximal to the Gastroesophageal Junction: A Case Report.

Gastric leiomyomas are benign, submucosal tumors found incidentally on unrelated imaging or during autopsy. The majority of leiomyomas are asymptomatic; however, patients can develop central ulcerations on the lesions leading to upper gastrointestinal (GI) bleeding. A 75-year-old female, with a past medical history of hypertension, hyperlipidemia, and a cerebrovascular accident, presented with complaints of melena, near-syncope events, lightheadedness, weakness, and hematemesis. A computed tomography (CT) of the abdomen with contrast found a heterogeneous low-attenuation mass of 4×4×3 cm3 within the gastric fundus and near the gastroesophageal (GE) junction. After an open gastrostomy and excisional biopsy, the mass was identified as a leiomyoma. This case report reviews the presentation, diagnostic assessments, and treatment of a gastric leiomyoma in a complex location proximal to the gastroesophageal junction. Gastric leiomyomas should be considered as a differential diagnosis for patients presenting with an upper gastrointestinal bleed.