Abstract

IntroductionThe aim of this study was to determine if the inflammation of the sympathetic ganglia (SG) in thromboangiitis obliterans (TAO) is induced by an infectious pathogen inside or if it is a reactive sterile inflammation.MethodsFor the purpose of this study, the gene expression of high-mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), toll-like receptor 9 (TLR9), and the receptor for advanced glycation end-products (RAGE) were evaluated on the complementary DNA (cDNA) of the SG tissues of 24 TAO patients and two controls with hyperhidrosis by real-time polymerase chain reaction (PCR) and analysed by the Pfaffl method.ResultsThe gene expression of HMGB1 and TLR9 increased by about 25- and 2-fold changes in the SG of the TAO patients, respectively. However, there was no change in the gene expression of TLR4 or RAGE.ConclusionIt appears that the inflammation in the SG of TAO patients is more likely a sterile inflammation, and its trigger may be mitochondrial DNA (mtDNA). Cadmium in cigarettes could be responsible for the induction of mtDNA release to the cell cytoplasm. In addition, the high expression of HMGB1 may play a role in the pathogenesis of TAO and may be responsible for both clinical manifestation of the disease and the imaging findings. Moreover, HMGB1 may be a target for treatment protocols for TAO. Further studies are highly recommended.

Highlights

  • The aim of this study was to determine if the inflammation of the sympathetic ganglia (SG) in thromboangiitis obliterans (TAO) is induced by an infectious pathogen inside or if it is a reactive sterile inflammation

  • The gene expression of high-mobility group box 1 (HMGB1) was found to increase by approximately 24-fold changes

  • Our results demonstrated that the gene expression of HMGB1 and toll-like receptor 9 (TLR9) increased about 25- and 2-fold changes in the SG of TAO patients, respectively

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Summary

Introduction

The aim of this study was to determine if the inflammation of the sympathetic ganglia (SG) in thromboangiitis obliterans (TAO) is induced by an infectious pathogen inside or if it is a reactive sterile inflammation. Thromboangiitis obliterans (TAO), or Buerger’s disease, is an inflammatory, thrombotic-occlusive, mediumand small-sized vasculitis that usually occurs in young males with a history of tobacco use [1]. The possible role of infectious pathogens as the trigger of TAO has been suggested [1]. In addition to oral bacteria pathogens, since the 1980s, the possibility of Rickettsia infection has been suggested as a trigger for TAO [5, 6]. Rickettsia infection was detected using PCR in 3 of 25 biopsies from a below-knee amputated limb in a TAO patient [7]. The antibodies for the Rocky Mountain spotted fever (RMSF) group were

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