Abstract

Tonsil tissue is a very important component of the human immunity system, contributing to the functioning of the cellular and humoral defence system, especially in childhood. The endoplasmic reticulum (ER) is an organelle that has a very important function in the balanced functioning of cells, in which the accumulation of a cellular protein called ER stress occurs in case of dysfunction. ER stress influences the pathogenesis of many diseases and immune system functions. We aimed to investigate the relation between the diseases of tonsil tissue and ER stress response to elucidate the mechanisms of diseases related with the immune system. A prospective study was conducted in 46 children aged between 2 and 16years who underwent tonsillectomy for chronic tonsillitis or tonsillar hypertrophy. Tonsil tissue was separated into two groups according to their size and evaluated in terms of ER stress markers and apoptosis markers by Real-time PCR and Western blot analysis. The ΔCT levels of ER stress markers (ATF4, ATF6, CHOP, GRP78, EIF2AK3, ERN1, GRP94) were greater in children with chronic tonsillitis (p < 0.005). In contrast, the tonsillar hypertrophy group had greater ΔCT levels of apoptosis markers (BAX, BCL-2) according to the Real-time PCR method (p < 0.005). According to the Western blot analysis, the normalized levels of ATF4, ATF6, CHOP, GRP78, and ERN1 genes were found greater in the chronic tonsillitis group than the tonsillar hypertrophy group. There was no difference between the two groups in terms of normalized BCL-2 and BAX levels by Western blot analysis. This is the first study in the literature investigating the effect of the ER stress pathway on the etiopathogenesis of tonsil diseases. It was concluded that the ER stress pathway plays a role in the etiopathogenesis of chronic tonsillitis. Investigating the relationship between ER stress and structures such as the tonsil tissue that make up the immune system can help create new treatment strategies. Trial Registration ClinicalTrials.gov Identifier: NCT04653376.

Highlights

  • Tonsil tissue, as a vital part of the Waldeyer ring, is an important component of the immune system located centrally at the entrance of respiratory and gastrointestinal systems, where pathogens, infectious agents, and allergens invading the upper respiratory tract first encounter the immune system [1]

  • According to the Western blot analysis, the normalized levels of ATF4, Activating transcription factor 6 (ATF6), C/EBP homologous protein (CHOP), GRP78, and ERN1 genes were found greater in the chronic tonsillitis group than the tonsillar hypertrophy group

  • It was concluded that the endoplasmic reticulum (ER) stress pathway plays a role in the etiopathogenesis of chronic tonsillitis

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Summary

Introduction

As a vital part of the Waldeyer ring, is an important component of the immune system located centrally at the entrance of respiratory and gastrointestinal systems, where pathogens, infectious agents, and allergens invading the upper respiratory tract first encounter the immune system [1]. Tonsil tissue is a secondary lymphoid organ that exerts both humoral and cellular immunity functions against various antigens with specific antibodies, B and T cell activities, and protects the body especially in young children [2]. In patients with tonsillitis, cellular, and humoral immune responses are stimulated together. Immunological reactions in tonsil tissue may give rise to chronic infections and hypertrophy. Hypertrophy may occur following bouts of local or systemic infection. They may undergo atrophy with chronic disease processes [2]

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