Apoptotic pathways of macrophages within osteolytic interface membrane in periprosthestic osteolysis after total hip replacement

Zhou

et al. 2019

J Exp Clin Cancer Res

Background Cysteine-rich intestinal protein 1 (CRIP1) is highly expressed in human intestine and aberrantly expressed in several types of tumor. However, studies on CRIP1 are limited and its role on tumor development and progression remains controversial and elusive. Methods Immunohistochemistry was performed to evaluate the expression of CRIP1 in paired normal and colorectal tumor specimens, as well as colorectal cell lines. Functional assays, such as CCK8, TUNEL assay and in vivo tumor growth assay, were used to detect the proliferation, apoptosis and response to 5-FU of CRIP1. Western blot was used to analyze Fas-mediated pathway induced by CRIP1. Rescue experiments were performed to evaluate the essential role of CRIP1 for Fas-mediated apoptosis. Results We demonstrated that CRIP1 is overexpressed in CRC tissues compared with adjacent normal mucosa. CRIP1 could dramatically recover the 5-Fluorouracil (5-FU) inhibited CRC cell proliferation in vitro and stimulate the tumor formation of CRC in vivo, probably through inhibiting CRC cell apoptosis. Moreover, CRIP1 also dramatically recovered the 5-Fluorouracil (5-FU) induced tumor cell apoptosis in vitro . Further study demonstrated that CRIP1 down-regulated the expression of Fas protein and proteins related to Fas-mediated apoptosis. CRIP1 could interact with Fas protein and stimulate its ubiquitination and degradation. In addition, a negative correlation was detected between the expression of CRIP1 and Fas protein in most of the clinical human CRC samples. Conclusion The current research reveals a vital role of CRIP1 in CRC progression, which provide a novel target for clinical drug resistance of colorectal cancer and undoubtedly contributing to the therapeutic strategies in CRC. Electronic supplementary material The online version of this article (10.1186/s13046-019-1117-z) contains supplementary material, which is available to authorized users.

Section: Discussionmentioning

confidence: 99%

Cysteine-rich intestinal protein 1 suppresses apoptosis and chemosensitivity to 5-fluorouracil in colorectal cancer through ubiquitin-mediated Fas degradation

Zhou

et al. 2019

J Exp Clin Cancer Res

“…In a human study investigating the effect of ER stress and apoptosis on osteolysis, ER stress and apoptosis were evaluated to cause loosening and loss of the prosthesis, and the apoptosis expression genes (BCL-2 and BAX) and ER stress markers (IRE1-α, GRP78 / Bip, CHOP, cleaved caspase-4, and JNK) expression levels were found to be signi cantly increased compared to the control group and there was a correlation between the degree of ER stress and the clinical severity of osteolysis. Thus, it was proven that ER stress exerts an impact on the apoptotic process in osteolysis [19]. Studies on human epithelial cells have investigated the role of ER stress in the development of epithelial-to-mesenchymal transition, in multiple tissues, including the eye, lungs, liver, and kidneys, and it has been revealed that ER stress triggers the development of epithelial-to-mesenchymal transition and causes pathological conditions [20].…”

Section: Discussionmentioning

confidence: 99%

Relationship of endoplasmic reticulum stress with the etiopathogenesis of chronic tonsillitis and tonsillar hypertrophy in pediatric patients: a prospective, parallel-group study

et al. 2021

Objectives: 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 in uences 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.Methods: A prospective study was conducted in 46 children aged between 2 and 16 years 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.Results: 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.Conclusion: This is the rst 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 Identi er: NCT04653376

“…Ti particles stimulate the gathering of macrophages cells to produce a variety of proinflammatory cytokines, such as TNF-α and IL-6, in interfacial membranes [ 28 – 30 ]. In addition, the fibrous interface membrane around a loosening periprosthetic shows a predominance of macrophages, which represent 60–80% of the entire cellular population [ 31 ]. In the present study, our results also indicated that Ti particles increased the macrophage population, which is consistent with previous reports.…”

Section: Discussionmentioning

confidence: 99%

Endotoxin Contributes to Artificial Loosening of Prostheses Induced by Titanium Particles

2018

Self Cite

BackgroundAseptic loosening of orthopedic implants caused by wear particles is a major cause of joint replacement failure. However, the mechanism of aseptic loosening has not yet been defined. The present study explored whether endotoxin adherent on the titanium (Ti) particles contributes to aseptic loosening.Material/MethodsLimulus amebocyte lysate detection was conducted to detect the levels of endotoxin adhered to the Ti particles. A mouse air pouches model was established and mice were divided into 4 groups and injected with phosphate-buffered saline (PBS) or Ti particles suspensions (0.1, 1, 10 mg/mL), following detection of the number of macrophages and the level of endotoxin. Scanning electron microscopy (SEM) was used to characterize the microstructures of Ti particles adhered with endotoxin.ResultsIn vitro experiments showed that the level of endotoxin adhered to the Ti particles was significantly increased after adding LPS back to these “endotoxin-free” particles. In vivo experiments showed that Ti particles injection significantly increased the number of macrophages and the level of endotoxin.ConclusionsIn conclusion, these results suggest that adherent endotoxin may play an important role in aseptic loosening induced by Ti particles.