Translationally controlled tumor protein exerts a proinflammatory role in acute rejection after liver transplantation

Hepatobiliary Pancreat Dis Int. 2020 Jun;19(3):235-243. doi: 10.1016/j.hbpd.2020.03.001. Epub 2020 Mar 12.

Abstract

Background: Translationally controlled tumor protein (TCTP), which has been verified to have a proinflammatory activity, plays an important role in allergy. However, it remains unclear whether TCTP has an impact on the acute rejection (AR) after liver transplantation.

Methods: Three protocols were used to delineate the role of TCTP in AR after liver transplantation. First, in rat orthotopic liver transplantation (OLT), the expression of TCTP was measured by enzyme-linked immunosorbent assay (ELISA), real-time PCR, Western blot and immunofluorescence assays. Second, in mixed lymphocyte reaction (MLR), the role of TCTP in lymphocyte proliferation was measured by carboxyfluorescein succinimidyl ester (CFSE) labeling and the impact of TCTP on inflammatory factor release was detected by cytokine arrays. Third, in human OLT, the level of serum TCTP was detected by ELISA, and the relationship between TCTP and model for early allograft function (MEAF) score was assessed by Spearman's correlation.

Results: In rat OLT, AR resulted in great harm to allografts, manifesting as deterioration of liver function, increasing inflammatory factors and infiltrating lymphocytes. Meanwhile, TCTP was overexpressed in serum and allografts. Higher level of TCTP was associated with higher rejection activity index (RAI). In an MLR protocol, TCTP knockdown inhibited the proliferation of mixed inflammatory cells and significantly suppressed the release of 15 cytokines and chemokines. In human OLT, the serum TCTP was up-regulated within a week after operation. Additionally, the increasing speed of serum TCTP positively correlated with MEAF scores (r = 0.449; P = 0.0088).

Conclusions: Up-regulated TCTP positively affects AR after liver transplantation.

Keywords: Acute rejection; Liver transplantation; Lymphocyte; Translationally controlled tumor protein.

MeSH terms

  • Acute Disease
  • Allografts / physiopathology
  • Animals
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism*
  • Cell Proliferation / genetics
  • Cytokines / metabolism*
  • Gene Knockdown Techniques
  • Graft Rejection / blood*
  • Graft Rejection / pathology
  • Graft Rejection / physiopathology
  • Humans
  • Inflammation / blood*
  • Liver / physiopathology*
  • Liver Transplantation
  • Lymphocyte Culture Test, Mixed
  • Lymphocytes / physiology
  • Male
  • RNA, Messenger / blood
  • Rats
  • Tumor Protein, Translationally-Controlled 1

Substances

  • Biomarkers, Tumor
  • Cytokines
  • RNA, Messenger
  • TPT1 protein, human
  • Tpt1 protein, rat
  • Tumor Protein, Translationally-Controlled 1