Jie Ma1,2, Chuanxi Chen1,2, Yongjun Liu2, Mahendra Damarla3, Becky M Vonakis1, Xiangdong Guan2, Li Gao1. 1. Division of Allergy & Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA. 2. Department of Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China. 3. Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Abstract
BACKGROUND: In sepsis, reorganization of the actin cytoskeleton in the epithelium during inflammation will lead to a breakdown of epithelial barrier integrity, and contribute to the pathogenesis of sepsis, but the exact changes of various components regulating the actin cytoskeleton pathway remain unclear. METHODS: We used lipopolysaccharide (LPS) challenged primary epithelial cells cultured at the air-liquid interface (ALI) to mimic epithelial barrier dysfunction during sepsis. Then we detected differential expression of T-lymphoma invasion and metastasis 1 (TIAM1) gene in lung epithelial cells and septic models. RESULTS: LPS induced barrier dysfunction in human tracheobronchial epithelial cells (HTBEs) as measured by statistically significant changes in ionic and macromolecular permeability. We observed differential expression of TIAM1 gene. The protein expression of TIAM1 was decreased after LPS challenge, in human bronchial epithelial cells. Furthermore, the expression levels of both TIAM1 mRNA and protein were decreased in lungs of septic rodent models. CONCLUSIONS: Given that expression levels of TIAM1 have been associated with mortality among sepsis patients, our findings have the potential for the development of diagnostic and treatment strategies relevant for patient management.
BACKGROUND: In sepsis, reorganization of the actin cytoskeleton in the epithelium during inflammation will lead to a breakdown of epithelial barrier integrity, and contribute to the pathogenesis of sepsis, but the exact changes of various components regulating the actin cytoskeleton pathway remain unclear. METHODS: We used lipopolysaccharide (LPS) challenged primary epithelial cells cultured at the air-liquid interface (ALI) to mimic epithelial barrier dysfunction during sepsis. Then we detected differential expression of T-lymphoma invasion and metastasis 1 (TIAM1) gene in lung epithelial cells and septic models. RESULTS: LPS induced barrier dysfunction in human tracheobronchial epithelial cells (HTBEs) as measured by statistically significant changes in ionic and macromolecular permeability. We observed differential expression of TIAM1 gene. The protein expression of TIAM1 was decreased after LPS challenge, in human bronchial epithelial cells. Furthermore, the expression levels of both TIAM1 mRNA and protein were decreased in lungs of septic rodent models. CONCLUSIONS: Given that expression levels of TIAM1 have been associated with mortality among sepsis patients, our findings have the potential for the development of diagnostic and treatment strategies relevant for patient management.
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