SIGIRR participates in negative regulation of LPS response and tolerance in human bladder epithelial cells.

Dan Li,Xin Zhang,Baiyi Chen

doi:10.1186/s12865-015-0137-5

Dan Li, Xin Zhang + Show 1 more

Open Access

https://doi.org/10.1186/s12865-015-0137-5

Copy DOI

Abstract

BackgroundThe innate immune response of urinary tract is critically important in the defense to microbial attack. Toll-like receptor 4 (TLR4) controls initial mucosal response to uropathogenic Escherichia coli (UPEC). However, excessive and dysfunctional TLR signaling may result in severe inflammation and inappropriate tissue damage. Previous studies have demonstrated that single immunoglobulin IL-1R-related receptor/Toll IL-1 receptor 8 (SIGIRR/TIR8) is a member of the toll-interleukin-1 receptor (TIR) family that can negatively modulate TLR4 mediated signaling, but its role in the innate immunity of urinary tract infection remains incompletely defined. In this study, we investigated its cellular distribution and mechanisms involved within the human bladder epithelial cells after LPS stimulation.ResultsImmunostaining, reverse transcription PCR and Western blot results showed that SIGIRR was constitutively expressed in the human bladder epithelial cell lines and was downregulated after LPS stimulation. To further define the role of SIGIRR, cells were transiently transfected with SIGIRR siRNA and stimulated with LPS. SIGIRR gene silencing augmented chemokine expression in response to LPS, as indicated by increased levels of IL-6 and IL-8 secretions in the supernatants compared with negative control siRNA. Furthermore, LPS tolerance, a protective mechanism against second LPS stimulation, was significantly reduced in SIGIRR siRNA transfected cells. Moreover, transient gene silencing augmented LPS-induced NF-κB and MAPK activation.ConclusionsIn conclusion, our results suggest that SIGIRR plays an important role in the negative regulation of LPS response and tolerance in human bladder epithelial cells, possibly through its impact on TLR-mediated signaling.

Highlights

The innate immune response of urinary tract is critically important in the defense to microbial attack
Induction of IL-6 and IL-8 secretions by LPS in human bladder epithelial cell lines The two human bladder epithelial cell lines were stimulated with LPS, and the levels of IL-6 and IL-8 in the culture supernatants were determined by ELISA
The results suggest that SIGIRR is constitutively expressed in nonstimulated cells (Fig. 2a and b)

Summary

Introduction

The innate immune response of urinary tract is critically important in the defense to microbial attack. Toll-like receptor 4 (TLR4) controls initial mucosal response to uropathogenic Escherichia coli (UPEC). Previous studies have demonstrated that single immunoglobulin IL-1R-related receptor/Toll IL-1 receptor 8 (SIGIRR/TIR8) is a member of the toll-interleukin-1 receptor (TIR) family that can negatively modulate TLR4 mediated signaling, but its role in the innate immunity of urinary tract infection remains incompletely defined. BECs can recognize conserved pathogen-associated molecular patterns (PAMPs) via several kinds of pattern recognition receptors (PRRs), including Toll-like receptors (TLRs) which can control the innate host defense at mucosal surfaces and protect the mucosal barrier against bacterial attack. Li et al BMC Immunology (2015) 16:73 in bladder epithelial cells including TLR4, which recognizes lipopolysaccharide (LPS) from Gram-negative bacteria and plays a key role in inducing the inflammatory responses elicited by UPEC [6,7,8,9,10,11]. Transcriptions of various cytokines were stimulated including IL-6 and IL-8, two of the major cytokines that are constitutively produced by urinary epithelial cells following the bacterial infection [14, 15]

Methods

Results

Discussion

Conclusion