Endoplasmic reticulum stress, unfolded protein response and altered T cell differentiation in necrotizing enterocolitis
| Autor: | Jiaping Mei, Anita M. Korteland-van Male, Johannes B. van Goudoever, Ingrid B. Renes, Peng Lu, Adrianus C. J. M. de Bruijn, Janneke Witte-Bouma, Marie-Chantal Struijs |
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| Přispěvatelé: | Pediatrics, Pediatric Surgery, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam Reproduction & Development (AR&D), Paediatrics, Pediatric surgery, ICaR - Circulation and metabolism |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
X-Box Binding Protein 1 Pathology medicine.medical_specialty XBP1 T-Lymphocytes Blotting Western Fluorescent Antibody Technique lcsh:Medicine Regulatory Factor X Transcription Factors Biology Polymerase Chain Reaction Statistics Nonparametric Enterocolitis Necrotizing Gene expression medicine Humans lcsh:Science Endoplasmic Reticulum Chaperone BiP DNA Primers Enterocolitis Multidisciplinary ATF6 Interleukin-6 Endoplasmic reticulum Interleukin-8 lcsh:R Infant Newborn FOXP3 Cell Differentiation medicine.disease Endoplasmic Reticulum Stress Immunohistochemistry digestive system diseases DNA-Binding Proteins Gene Expression Regulation Necrotizing enterocolitis Unfolded protein response Unfolded Protein Response Female lcsh:Q medicine.symptom Infant Premature Transcription Factors Research Article |
| Zdroj: | PLoS ONE, Vol 8, Iss 10, p e78491 (2013) Lu, P, Struijs, M C, Mei, J P, Witte-Bouma, J, Korteland-van Male, A M, de Bruijn, A C J M, van Goudoever, J B & Renes, I B 2013, ' Endoplasmic Reticulum Stress, Unfolded Protein Response and Altered T Cell Differentiation in Necrotizing Enterocolitis ', PLoS ONE, vol. 8, no. 10, e78491 . https://doi.org/10.1371/journal.pone.0078491 PLoS One (print), 8(10). Public Library of Science PLoS ONE PLoS ONE, 8(10). Public Library of Science PLoS ONE, 8(10):e78491. Public Library of Science |
| ISSN: | 1932-6203 |
| Popis: | textabstractBackground:Endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) play important roles in chronic intestinal inflammation. Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm infants and is characterized by acute intestinal inflammation and necrosis. The objective of the study is to investigate the role of ER stress and the UPR in NEC patients.Methods:Ileal tissues from NEC and control patients were obtained during surgical resection and/or at stoma closure. Splicing of XBP1 was detected using PCR, and gene expression was quantified using qPCR and Western blot.Results:Splicing of XBP1 was only detected in a subset of acute NEC (A-NEC) patients, and not in NEC patients who had undergone reanastomosis (R-NEC). The other ER stress and the UPR pathways, PERK and ATF6, were not activated in NEC patients. A-NEC patients showing XBP1 splicing (A-NEC-XBP1s) had increased mucosal expression of GRP78, CHOP, IL6 and IL8. Similar results were obtained by inducing ER stress and the UPR in vitro. A-NEC-XBP1s patients showed altered T cell differentiation indicated by decreased mucosal expression of RORC, IL17A and FOXP3. A-NEC-XBP1s patients additionally showed more severe morphological damage and a worse surgical outcome. Compared with A-NEC patients, R-NEC patients showed lower mucosal IL6 and IL8 expression and higher mucosal FOXP3 expression.Conclusions:XBP1 splicing, ER stress and the UPR in NEC are associated with increased IL6 and IL8 expression levels, altered T cell differentiation and severe epithelial injury. |
| Databáze: | OpenAIRE |
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