Login to Access Video or Poster Abstract: MP06-10
Sources of Funding: none

Introduction

Inflammation amplifier (IA), a local chemokine inducer in non-immune cells is induced by the simultaneous activation of NF?B and STATs (IL-17, TNF?, and IL-6) and leads to a synergistic production of chemokines, growth factors, and cytokines. IA was essential for the development of inflammation in various autoimmune disease models. More recently, IA was critical for the development of chronic rejections both in murine models and human allogeneic lung transplantations (J Immunol. 189, 1928 and Int. Immunol. 25, 319). The status of IA can be a new biomarker and its regulator can be a new therapeutic target in rejected kidney allografts (KA). The objective of this study was to investigate the contribution of IA during the rejection process in KA and to identify genes regulating IA.

Methods

Primary human kidney cells (PHKC) were stimulated with IL-17, IL-6, TNF?, and expressions of chemokines and IL-6 were measured by RT-PCR. Among the genes highly expressed in PHKC with IA activation, we focused on a gene named Renal NFkB Enhancer-1 (RNE1). A deficiency of RNE1 suppressed chemokines and IL-6 after IA activation in PHKC, indicating that RNE1 might be a positive regulator in IA. In another experiment, urinary RNE1 in kidney transplant recipients (KTR) were measured by ELISA and clinical data (serum creatinine, CRP, urinary protein, urinary albumin, urinary NAG, and eGFR) were also compared among the KTR patient groups with normal histology, interstitial fibrosis and tubular atrophy (IF/TA), or chronic active antibody-mediated rejection (CAAMR).

Results

PHKC expressed excess amounts of chemokines and IL-6 after IA activation by IL-17, IL-6, and TNF?. Urinary RNE1 in KTR showed significantly higher amount in CAAMR patients (48606 ng/mgCre, n=9) compared to IF/TA (10744 ng/mgCre, n=21) and normal (6081 ng/mgCre, n=13). In contrast, serum creatinine, CRP, eGFR, U-NAG levels showed no significant difference among patient groups.

Conclusions

IA was activated in PHKC, and urinary RNE1 was elevated in rejected KA. These results suggested that activation of IA is involved in KA rejection, and RNE1 could be a new biomarker. Now, we are planning to examine detailed molecular mechanisms how RNE1 regulates NF-kB pathway in kidney cells and to examine if it will be a new therapeutic target for allogeneic kidney transplantations._x000D_ _x000D_

Funding

none