Toll-Like Receptor 4 as an Immune Receptor Against Mycobacterium tuberculosis: A Systematic Review.

OBJECTIVE: To review the main Mycobacterium tuberculosis (Mtb) pathogen-associated molecular patterns (PAMPs) and the roles played by toll-like receptor (TLR)4 in determination of Mtb infection outcome. METHODS: Several scientific databases, including Scopus, PubMed, and Google Scholar, were used for searching appropriate research articles from the literature for information on our topic. RESULTS: TLR4 plays positive roles in induction of immune responses against Mtb and participates in eradication of the infection. Some limited investigations approved the roles of TLR4 in induction of apoptosis in macrophages during tuberculosis (TB) and attenuation of immune responses in some situations. CONCLUSIONS: TB outcome appears to be dependent on TLR4/Mtb interaction and several factors, including bacterial load and immune or nonimmune cells, as hosts. Also, other TLR/Mtb interactions can affect TLR4 responses.

Comparison of serum levels of IL-6, IL-8, TGF-ß and TNF-α in coronary artery diseases, stable angina and participants with normal coronary artery.

Cytokines, which typically regulate the immune responses, play a role in cardiovascular diseases such as coronary artery diseases (CAD) and ischemic heart diseases (IHD). The aims of this study were to evaluate serum levels of IL-6, IL-8, TGF-ß and TNF-α in patients with or without CAD, as well as stable angina, and to assess the effects of drug administration on the serum levels of these cytokines. Serum levels of the cytokines were analyzed in the three groups: patients with acute coronary syndrome, stable angina and participants with normal coronary arteries as controls. Cohort study of the patients showed that Nitrocontin was the only drug used in a significantly different pattern between the groups where it was used less frequently in patients with stable angina compared to the acute coronary syndrome or control groups. Serum levels of the evaluated cytokines were not different neither between the studied groups nor between the groups with variable Gensini scores. However, IL-8 in controls that were not engaged in regular exercise was higher than the controls performing regular exercise. In the stable angina group, TNF-α in non-smokers was higher than the smokers. It was revealed that serum levels of pro-inflammatory cytokines are not associated with atherosclerosis and stable angina in patients from the South-East of Iran. However, suppressed expression of TGF-ß, may increase the risk of CAD. Exercise can reduce the risk of CAD through downregulation of pro-inflammatory cytokines.

Inflammasomes and type 2 diabetes: An updated systematic review.

Type 2 diabetes (T2D) is a metabolic disorder that is accompanied by chronic inflammation. The main mechanisms and molecular signaling of the induction of inflammation in T2D are still unknown. It seems that intracellular sensors that participate in recognition of endogenous damage associated molecular patterns (DAMPs) play key roles in the induction/stimulation of chronic inflammation in T2D. The Nucleotide-binding oligomerization domain, Leucine-rich Repeat and Pyrin domain containing (NLRP) family and accompanying Inflammasomes are important intracellular receptors of inflammatory pathogens and stress signals that elevate caspase-1-mediated release of IL-1ß and IL-18. Studies suggest that disruption of NLRP1 and NLRP3 has a major role for these inflammasomes in internal immunity and inflammation as well as metabolic disorders. Thus, it seems that these mediators may participate in the induction/stimulation of chronic inflammation in patients. This systematic review provides an up-to-date evaluation of our current understanding of the roles of inflammasomes in the pathogenesis of T2D and its complications.

Toll like receptor 4 and hepatocellular carcinoma; A systematic review.

INTRODUCTION: Toll like receptor 4 (TLR4) is an extracellular pathogen recognition receptor (PRR) which recognizes a wide range of pathogens and damage associated molecular patterns (PAMPs and DAMPs). It can activate intracellular signaling and consequently transcription factors which participate in transcription from either immune related or malignancy genes. Thus, it has been hypothesized that TLR4 may be a cause of hepatocellular carcinoma (HCC). This article has reviewed the roles of TLR4 in the pathogenesis of HCC. METHOD: "TLR4", "hepatocellular carcinoma", "liver tumor" and "liver cancer" were used as key words for searching in Scopus, Google Scholar and MEDLINE scientific databases. RESULTS: Most of the investigations documented the roles of TLR4 in induction of HCC via several mechanisms including increased number of T regulatory lymphocytes and liver resident follicular helper like cells, increased production of pro-inflammatory and malignancy related molecules including cytokines, NANOG, Caspase-1, Ephrin-A1, NO and BCL6. TLR4 participates in the proliferation of the cells and also production of the molecules in both chronic infectious and non-infectious inflammatory diseases. DISCUSSION: TLR4 is an innate immunity receptor which plays a pathogenic role during chronic inflammation and can induce HCC in human.

Correction: Atorvastatin, Losartan and Captopril Lead to Upregulation of TGF-ß, and Downregulation of IL-6 in Coronary Artery Disease and Hypertension.

[This corrects the article DOI: 10.1371/journal.pone.0168312.].

A Cross-Sectional Study of Glycemic Status and Zinc Level in Patients with Beta-Thalassemia Major.

Background: Endocrinopathies and diabetes mellitus are prevalent in patients with beta-thalassemia major Recently some studies demonstrate a link between low levels of serum zinc level and higher prevalence of diabetes. The aim of this study was to evaluate the glucose tolerance in patients suffered from beta-thalassemia major and determine the association of Homeostasis Model Assessment (HOMA) parameters with zinc status among these patients. Materials andMethods: In this cross sectional study, clinical data of patients who were suffered from thalassemia major, aged≥10 years were collected. Serum ferritin concentration, fasting blood sugar, fasting blood insulin and serum zinc level were assessed after overnight fasting. Moreover, oral glucose tolerance test was performed. Homeostasis Model Assessment (HOMA-2) was used for calculating beta-cell function, insulin resistance and sensitivity for normoglycemic and pre-diabetic subjects. Results: of the 163 patients diagnosed with beta-thalassemia major, 10%, 53% and 37% were diabetic, pre-diabetic and normal, respectively. Mean serum zinc concentration was equal to 18.90±10.93µg/dl, and it was not significantly different across diabetic, pre-diabetic and normal groups. Pre-diabetic patients had significantly lower beta-cell function compared to normal subjects (P=0.0001). An inverse relation was documented between beta-cell function on one hand and total units of blood transfusion and ferritin level on the other hand (r=-0.29, P=0.004 and r=-0.27, P=0.03, respectively). The analysis adjusted for multiple possible confounders showed that there is no significant association between HOMA parameters and serum zinc level. Conclusion: Impaired glucose metabolism and low serum zinc level were quite common among our study participants. The findings of the study also signifies the substantial role of follow-up in early detection and appropriate treatment.

Atorvastatin, Losartan and Captopril Lead to Upregulation of TGF-ß, and Downregulation of IL-6 in Coronary Artery Disease and Hypertension.

INTRODUCTION: Coronary artery disease (CAD) and hypertension are the main reasons of ischemic heart diseases (IHDs). Cytokines as the small glycoproteins are the main arm of immune system and manipulate all of the cardiovascular diseases. The aim of the current study was to examine the effects of treatment of hypertension and CAD on serum levels of IL-6, IL-8, TGF-ß and TNF-α. MATERIAL AND METHODS: This interventional study was performed on the patients with hypertension without CAD (group 1), hypertension and CAD (group 2), CAD but not hypertension (group 3) and without hypertension and CAD as controls (group 4). The patients received routine treatment for hypertension and CAD. Serum levels of IL-6, IL-8, TGF-ß and TNF-α were analyzed in the groups treated with various drugs, using ELISA technique. RESULTS: With regard to the medications, Atorvastatin, Losartan and Captopril were administered more in patients (groups 1, 2 and 3) than the patients without hypertension and CAD. The results revealed that serum levels of TGF-ß and IL-6 were significantly increased and decreased, respectively, in the groups 1, 2 and 3 when compared to group 4. Serum levels of TGF-ß were also increased in females in comparison to males in the group 4. DISCUSSION: According to the results it seems that Atorvastatin, Losartan and Captopril have reduced inflammation in in vivo conditions via downregulation of IL-6 and upregulation of TGF-ß.

Toll-like receptor 2 and type 2 diabetes.

Innate immunity plays a crucial role in the pathogenesis of type 2 diabetes and related complications. Since the toll-like receptors (TLRs) are central to innate immunity, it appears that they are important participants in the development and pathogenesis of the disease. Previous investigations demonstrated that TLR2 homodimers and TLR2 heterodimers with TLR1 or TLR6 activate innate immunity upon recognition of damage-associated molecular patterns (DAMPs). Several DAMPs are released during type 2 diabetes, so it may be hypothesized that TLR2 is significantly involved in its progression. Here, we review recent data on the important roles and status of TLR2 in type 2 diabetes and related complications.