Date: Monday, June 13, 2016
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Halls C&D
Introduction: Inflammation amplifier (IA), a local chemokine inducer in non-immune cells is induced by the simultaneous activation of NFκB and STATs (IL-17, TNFα, 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).
Objective: The objective of this study was to investigate the contribution of IA during the rejection process in kidney allografts to obtain new therapeutic targets.
Materials and Methods: Immunohistochemistry (IHC) was performed to determine the expression of phosphorylated STAT3 and p65 (NFκB) in biopsy samples (Bx samples) of transplanted kidneys diagnosed as chronic active antibody-mediated rejection (CAAMR) or normal pathology. In in vitro assay, primary human kidney cells including tubular epithelial cells (TEC) and, glomerular microvascular endothelial cells (GMEC)) were stimulated with IL-17, IL-6, and TNFα and investigated for gene expressions of chemokines and IL-6 by RT-PCR. RT-PCR and/or RNA sequence analysis were also performed in primary TEC and GMEC isolated from normal human kidneys and Bx samples.
Results: IHC of Bx samples showed that simultaneous activation of NFκB and STAT was present in glomeruli and tubules. The degree of IA activation was greater in allografts with CAAMR compared to normal ones, suggesting the involvement of IA activation in the chronic rejection of kidney allografts. Consistent with these results, human primary TEC and GMEC expressed excess amounts of chemokines and IL-6 after stimulation by IL-17, IL-6, and TNFα.
Conclusion: IA was activated in glomeruli and tubules in CAAMR but not in non-rejected kidneys. IA in human primary cells in glomeruli and tubules is activated after cytokine stimulation. These results suggested that activation of IA is involved in chronic rejection. Now, we are seeking genes that regulate IA in the development of chronic rejection in kidney allografts.
CITATION INFORMATION: Higuchi H, Bando H, Jing-Jing J, Atsumi T, Iwami D, Morita K, Shinohara N, Murakami M. Inflammation Amplifier, a Chemokine Inducer in Non-Immune Cells in Kidney Transplantation Graft. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Higuchi H, Bando H, Jing-Jing J, Atsumi T, Iwami D, Morita K, Shinohara N, Murakami M. Inflammation Amplifier, a Chemokine Inducer in Non-Immune Cells in Kidney Transplantation Graft. [abstract]. Am J Transplant. 2016; 16 (suppl 3). http://atcmeetingabstracts.com/abstract/inflammation-amplifier-a-chemokine-inducer-in-non-immune-cells-in-kidney-transplantation-graft/. Accessed November 20, 2017.
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