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.

CARD9 gene silencing with siRNA protects rats against severe acute pancreatitis: CARD9‐dependent NF‐κB and P38MAPKs pathway

“…This is therefore the first report to demonstrate that CARD9 expression is up-regulated in aseptic SAP and corresponds to previous findings [5]. In this study, it was found that CARD9 is overexpressed in SAP patients and was identified as a potential molecular marker due to its close correlation with the outcome and severity of pancreatic injury in SAP patients [5]. It has previously been shown that an up-regulation of CARD9 expression in SAP patients is associated with an upstream activation of the NF-jB and P38MAPK pathways [5].…”

“…To the best of our knowledge, the early course of SAP is characterized by non‐infectious inflammation. This is therefore the first report to demonstrate that CARD9 expression is up‐regulated in aseptic SAP and corresponds to previous findings . In this study, it was found that CARD9 is overexpressed in SAP patients and was identified as a potential molecular marker due to its close correlation with the outcome and severity of pancreatic injury in SAP patients .…”

“…Without any infections associated with micro‐organisms at the onset of disease, SAP has generally been regarded as being linked to sterile inflammation . It has previously been found that CARD9, NF‐κB and P38MAPK expression is up‐regulated in SAP patients . These data strongly suggest a potential mechanism through which NF‐κB and P38MAPK molecules are activated by the up‐regulated expression of CARD9 in SAP.…”

“…In this study, it was found that CARD9 is overexpressed in SAP patients and was identified as a potential molecular marker due to its close correlation with the outcome and severity of pancreatic injury in SAP patients [5]. It has previously been shown that an up-regulation of CARD9 expression in SAP patients is associated with an upstream activation of the NF-jB and P38MAPK pathways [5]. It has previously been reported that NF-jB and P38MAPK is responsible for regulating the transcription of a wide variety of genes involved in the development of SAP [6,7].…”

CARD9 as a potential target in cardiovascular disease

“…Dysregulated CARD9 signaling has been implicated in autoimmune diseases of the eye,28 contact hypersensitivity,29 and aseptic acute pancreatitis 30. CARD9 is a strong therapeutic candidate for multiple reasons.…”