Background: Paroxetine is one of the well-known antidepressants. Recent studies have focused on paroxetine’ s probable immuno-modulatory effects, since findings have indicated inflammation’ s role in the pathophysiology of depression. Therefore, in the present study, TLR2 and TLR4 mRNA genes expression was assessed in paroxetinetreated peripheral blood mononuclear cells (PBMCs). Methods: Venous blood samples were drawn from five healthy men (20-40 years old). Peripheral blood mononuclear cells (PBMCs) were isolated from samples and were cultured. After the first incubation for 24h, phytohemagglutinin plus lipopolysaccharide were added to the cells and then were incubated for 24h. Thereafter, cells were treated with different concentrations of paroxetine in the presence or absence of inhibitors of 5-HT2 and 5-HT7 receptors. After incubation for 48h, RNA was extracted and cDNA was synthesized. Using the real-Time PCR technique, TLR2 and TLR4 genes mRNA expression were evaluated. Statistical analysis of data were carried out using GraphPad Prism 7. Results: TLR2 and TLR4 mRNA expression were significantly increased in response to paroxetine at all concentrations. Furthermore, the co-culture of cells with the drug and the 5-HT2R and 5HT7R inhibitor simultaneously revealed that paroxetine’ s immuno-modulatory effects via TLR2 are dependent on serotonin, while it is independent of serotonin in the case of TLR4. Conclusion: Considering paroxetine’ s effect in modulating immune responses via increasing TLR2 and TLR4 expression, paroxetine could have therapeutic potentials in diseases with a deficiency in these receptors.

Background: Substance abuse leads to blood-brain barrier dysfunction and activation of neuro-inflammatory pathways. However, the contribution of serum levels of Toll-like receptor 2 (TLR-2) and S100 calcium-binding protein B (S100B) to neuropsychological outcomes has not been clearly established. This study aims to explore the relationship between TLR-2 and S100B serum concentrations in individuals with substance abuse and their potential influence on neuropsychological results, specifically regarding the functioning of the frontal lobe. Methods: This study involved 28 individuals who were diagnosed with substance abuse at Loghman Hakim Hospital’s Toxicology Unit in 2022. Serum TLR-2 concentration and S100B levels, as neuroinflammatory markers, and the frontal assessment battery (FAB), as executive function markers, were measured. Results: Substance abuse patients exhibited elevated levels of both TLR-2 and S100B. In drug addicts, a strong positive relationship was detected between serum levels of TLR-2 and S100B (r=0.742, P=0.0021) levels. Nevertheless, no significant relationship was found between FAB scores and serum concentrations of S100B and TLR-2. Conclusion: This study reveals increased serum TLR-2 and S100B levels in individuals with substance abuse. However, these elevated levels did not appear to be associated with risk factors related to substance abuse or frontal lobe function.

Objective: Toll-like receptors (TLRs) on Sertoli cells are thought to have essential roles in sperm protection. This study was conducted to investigate the expression of TLR2 and TLR3 in Sertoli cells of men with azoospermia.Materials and Methods: In this experimental study, testicular biopsies were taken from ten azoospermic men. Following enzymatic dissociation, the samples were moved to lectin coated petri dishes. After a few passages, all cells were cultivated and Seroli cells were sorted by flow cytometry. To confirm Sertoli cell purification, alkaline phosphatase activity (ALP) and immunohistochemistry assays were employed.The expression of TLR2 and TLR3 at the transcript and protein levels was examined with real-time quantitative reverse transcription-polymerase chain reaction (RT-QPCR) and western blot, respectively.Results: Isolation, purification and cultivation of human Sertoli cells were performed successfully. Efficacy of purification of Sertoli cells by fluorescence-activated cell sorting (FACS) sorter was ~97%. The type of cultured cells was confirmed by vimentin and follicle-stimulating hormone (FSH) receptor markers. Furthermore, the existence of anti-Müllerian hormone in culture was confirmed. RT-PCR showed that both genes were expressed in Sertoli cells. Consistently, proteins of both were also expressed in Sertoli cells.Moreover, QPCR showed that the relative expression of TLR3 transcripts was significantly higher than TLR2 in Sertoli cells. Although both genes are expressed in fibroblast cells, their level of expression was significantly lower than in Sertoli cells.Conclusion: This study confirmed expression of TLR2 and TLR3 in human Sertoli cells. This may be an indicator of their roles in developing immunity against pathogens as well as allo- and auto-antigens or viral antigens in seminiferous tubules.

Background: Toll-like receptors (TLRs), especially TLR2, play an important role in the immune responses of patients with tuberculosis (TB). The prevalence of TB is estimated 38. 15 per 100, 000 population in Golestan Province, Iran, which is higher than the rates reported in other provinces. Objectives: The current study aimed at detecting Arg677Trp and Arg753Gln polymorphisms in TLR2 genes detected in patients with TB in Golestan province. Methods: A total of 130 blood samples were collected from patients with sputum smear-positive TB, and 130 blood samples were collected from healthy individuals. Twopolymorphisms of TLR2 gene, i e, Arg677TrpandArg753Gln, were investigated via polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) and sequencing methods. Results: History of corticosteroid use was more frequently reported in patients, compared to the controls, while the frequency of Bacillus calmette-guerin (BCG) vaccination was more reported in controls. PCR-SSCP analysis of the TLR2 Arg677Trp region showed an almost identical pattern for patients and controls, while 2 SSCP patterns were observed in the amplicon, related to the Arg753Gln polymorphism. DNA sequencing for the Arg677Trp polymorphism showed a duplicated pseudogene, similar to the mutant sequence (C> T), as this polymorphism cannot be considered conclusive. The Arg753Gln polymorphism was not found in the samples, although nucleotide deletion (G) was detected at position 808 among the patients. Conclusions: The Arg753Gln polymorphism was not involved in susceptibility to TB in the current study population. The presence of pseudogenes in some genes such as TLR2 necessitates careful interpretation of such studies.

Introduction: Breast cancer is one of the most important causes of mortality in women. Various factors are involved in the development of cancer, including viruses. Toll-like receptors (TLRs) have an essential role in the innate immune system. The present study investigated the relationship between TLR2 rs5743708 polymorphisms and Torque teno virus (TTV) infection with breast cancer. Methods: Blood samples from 80 women with breast cancer and 80 healthy women were collected, and after DNA extraction, the presence of TTV was investigated by a PCR assay and polymorphism in the TLR2 gene (rs5743708) was explored using the PCR-RFLP method. Also, the physical and chemical properties of TLR2 protein in the two wild and mutant forms were analyzed using the ExPASy database. Results: Statistical analysis showed that there was no significant relationship between the age and TTV infection; TTV infection and breast cancer; the grade of cancer, and TTV infection; while there were significant relationships between rs5743708 polymorphisms and breast cancer; GG genotype and increased incidence of cancer; TTV infection and rs5743708 polymorphisms. Also, instability index, aliphatic index, grand average of hydropathicity, and molecular weight of TLR2 protein varied in wild and mutant states. Conclusions: Although there was no significant relationship between TTV infection and breast cancer, the rs5743708 polymorphisms might be involved in TTV infection and breast cancer.

Background: Toll like receptor-2 (TLR2) plays an important role in the process of detection and launching the immune response against Candida albicans. Cyclophosphamide is one of the most widely used chemotherapy drugs, which causes severe neutropenia and suppression of the immune system. In this study Balb/c mice were infected to disseminated candidiasis and neutropenia and expression of TLR2 gene was measured in whole blood samples of each mice.Methods: Twenty-eight mice were divided into 4 groups and injected with Cyclophosphamide and C. albicans.Blood samples were used for RNA extraction and cDNA synthesis, and expression of TLR2 gene was measured by real-time polymerase chain reaction (Real-time PCR). Statistical analysis was performed using Kruskal-Wallis and 2-DDCT method.Findings: Gene expression was increased in the group receiving Candida albicans and also in group receiving both Cyclophosphamide and Candida albicans but decreased in the group just receiving Cyclophosphamide.Conclusion: There was no significant difference between the control group and experimental groups for TLR2 gene expression (P=0.478). However, the results of this study can be regarding in selecting TLR2 or its receptor as a therapeutic target with monoclonal antibodies or gene therapy techniques.

Background: B. thetaiotaomicron is introduced as a candidate for the next generation of probiotics. TLR2, 4 play an important and necessary role in activating and modulating the innate immune system after exposure to bacteria in the intestine. This study aimed to investigate the effect of B. thetaiotaomicron and its derivatives on the alteration of the tlr2 and tlr4 gene expression. Materials and methods: The effects of B. thetaiotaomicron, OMVs, inactive bacteria and supernatant treatments on the tlr2 and tlr4 gene expression in the STC-1 cell line were investigated using the qRT-PCR method. Results: The treatment of the STC-1 cell line with live and active B. thetaiotaomicron did not have significant effect on transcription of tlr2, 4. The OMVs of this bacterium at 50 μ, g/ml significantly increased the gene expression of tlr2 (p=0. 01) and tlr4 (p=0. 02), but at a concentration of 100 μ, g/ml, its effect was not significant. Inactive bacteria at MOI 10 (p=0. 03) and MOI 50(p=0. 003) significantly induce the transcription of both two genes. Supernatant 25% significantly increased tlr2 (p=0. 038) and tlr4 (p=0. 034) gene expression at the transcription level. Conclusion: Our results showed that OMVs at a concentration of 50 μ, g/ml, inactive bacteria, and supernatant B. thetaiotaomicron play an important role in modulating immune response and can be used as a next generation postbiotics and paraprobiotic candidates for further studies to be used.