Glucocorticoid-induced Tumor Necrosis Factor Receptor Ligand Aggravates Lipopolysaccharide-induced Inflammation by Down-regulating the Programmed Death Ligand in Kupffer Cells

Author(s): Kun Xu, Yan Zhang, Si-dong Wei, Pei-zhi Li, Kun He, Jian-ping Gong, Chun Huang

Journal Name: Current Signal Transduction Therapy

Volume 10 , Issue 1 , 2015

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Objective: To investigate the mechanism of GITRL on regulating the inflammatory reaction through the programmed death ligand (PDL1) in Kupffer cells (KCs).

Methods: The KCs and the T cells were isolated and divided into 6 groups: (1) the Control group; (2) LPS group; (3) LPS+Control siRNA group, transfected with Control siRNA; (4) LPS+GITRL siRNA group, transfected with GITRL siRNA; (5) LPS+pEGFP-N1 control plasmid group, transfected with control plasmid; and (6) LPS+pEGFP-N1-GITRL plasmid group, transfected with GITRL plasmid. The control group was co-cultured in DMEM only, whereas all of the other groups were co-cultured with LPS (1 ug/m1). After 24 h of treatment, the expression levels of the TNF-α, GITRL, and PDL1 in the supernatant, proliferation and apoptosis of T cells and the transposition of P65 in KCs were evaluated.

Results: The GITRL expression in KCs was obviously increased after LPS-stimulation in comparison to the control group. Concurrently, PDL1 was inhibited, the T cells proliferated, and TNF-α levels in the supernatant were obviously increased in the LPS group. With GITRL gene silencing, the restraint on PDL1 was clearly decreased, and the indexes of inflammation were not as obvious as in the LPS group. Furthermore, the results of the pEGFP-N1-GITRL group were opposite from that of the GITRL silencing group. However, the inflammation was exacerbated with the lower PDL1 expression.

Conclusions: Increasing the expression of GITRL in the KCs may promote the proliferation of T cells by restraining PDL1, thus aggravating the inflammatory reaction. GITRL silencing could tilt the immunologic balance back and restraining the inflammatory reaction.

Keywords: Glucocorticoid-induced tumor necrosis factor receptor ligand, kupffer cell, LPS, programmed death ligand, T cell.

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Article Details

Year: 2015
Published on: 11 May, 2015
Page: [63 - 72]
Pages: 10
DOI: 10.2174/1574362410666150512004151

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