title: The role of Card9 overexpression in peripheral blood mononuclear cells from patients with aseptic acute pancreatitis.
abstract: Activated mononuclear cells are an early event in the course of severe acute pancreatitis (SAP). To date, the molecular mechanism triggering peripheral blood mononuclear cells (PBMCs) is poorly understood. The aim of this paper was to determine the potential role of Card9 in SAP. We collected data from 72 subjects between January 2013 and June 2014. Subsequently, PBMCs were isolated on day 1, 3 and 5 of pancreatitis. Immunofluorescence staining, quantitative real-time PCR, Western blotting, immunoprecipitation and ELISA were used to determine the role of Card9 in SAP. Microbial culture showed that SAP patients at the early period did not develop any bacteria and fungi infection. Card9 expression in SAP patients was higher than that in mild acute pancreatitis and volunteer healthy controls, up to the peak on day 1. The monocyte-derived cytokines interleukin (IL)-17, IL-1β, IL-6 and tumour necrosis factor-α mediated by the induction of Card9 markedly increased in SAP patients compared with the control group. Furthermore, the inducible formation of Card9-Bcl10 complex was found in PBMCs, which may be involved in nuclear factor kappa B (NF-κB) and p38 activation in SAP. Receiver operating characteristic curve indicated that Card9 levels had a high sensitivity of 87.5% and specificity of 67.7%, showing the close correlation with SAP patients. Card9 overexpression was firstly found in aseptic SAP, which may be played an important role in NF-κB and p38 activation in PBMCs. It also provided the new insights into therapeutic interventions by targeting monocytes activation in SAP patients.
authors.affiliation: Department of Pharmacy, Songjiang Hospital Affiliated Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhi-wen
authors.initials: ZW
authors.lastname: Yang
authors.affiliation: Department of Digestive, Shanghai Songjiang Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: Cheng-zhao
authors.initials: CZ
authors.lastname: Weng
authors.affiliation: Department of Digestive, Songjiang Hospital Affiliated Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Digestive, Shanghai Songjiang Hospital Affiliated to Nanjing Medical University, Nanjing, China.|Department of Digestive, Songjiang Hospital Affiliated Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D053468:CARD Signaling Adaptor Proteins / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D005260:Female; D015870:Gene Expression; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D010195:Pancreatitis / Q000097:blood* / Q000175:diagnosis / Q000276:immunology; D012372:ROC Curve; D015533:Transcriptional Activation
chemical_list: D015415:Biomarkers; D053468:CARD Signaling Adaptor Proteins; C505855:CARD9 protein, human; D016207:Cytokines; D016328:NF-kappa B
keywords: Card9 overexpression; acute pancreatitis; non-infection inflammation; peripheral blood mononuclear cells