Anti-TLR2 monoclonal antibody, clone TLR2.3 [FITC]

Background Altered innate immune function plays an important role in the initiation of inflammatory response in Behcet's disease (BD). Toll-like receptors (TLRs) are the master regulators of the innate immune system. Because the role of TLRs remains unknown in the pathogenesis of BD, the present study aimed to evaluate the expression levels and methylation status of the TLR2 and TLR4 promoters in patients with BD. Methods In the present study, Iranian Azeri BD patients (n= 47) with an active (n= 22) and inactive (n= 25) period, and healthy controls (n= 61), were matched according to age, sex and ethnicity. TLR2 and TLR4 genes promoter CpG islands were predicted with the Eukaryotic Promoter Database (https://epd.vital-it.ch). Methylated DNA immunoprecipitation (MeDIP) was conducted. Results The results showed that mRNA of TLR4 was significantly increased in the peripheral blood mononuclear cells (PBMCs) of BD patients with an active phase compared to the control group. Differences in mRNA of TLR4 between the inactive BD and control groups were not significant. Differences in TLR2 mRNA levels in the PBMCs of the active and inactive phase BD and control groups were not significant. The methylation rate of TLR4 gene promoter was significantly lower in the active and inactive BD groups compared to the control group. The difference between the active and inactive BD groups was not significant. There was no significant difference in the methylation rates of the TLR2 gene between studied groups. Conclusions Our preliminary findings suggest that the hypomethylation of TLR4 gene may be involved in the pathogenesis of BD via increasing TLR4 expression.

Doxorubicin (DOX) is widely used to treat multiple of tumors, but its clinical trials are allied with some serious adverse events mainly cardiac functional abnormalities. So the objective of our investigation is to identify the cardioprotective action of crocin (CRO), a natural compound derived from saffron, against DOX-induced cardiotoxicity. CRO was injected intraperitoneally (i.p.) to rats for six consecutive days and DOX (i.p.) was administered on the fourth day. H9c2 cells were treated with DOX for 24 h after being pre-treated by CRO for 2 h. CRO reduced tachycardia and J-point elevation, decreased the levels of serum creatine kinase, lactate dehydrogenase, glutamic-oxalacetic transaminase and glutamic-pyruvic transaminase. CRO exerted positive effect on DOX-induced ROS production and changes of oxidative stress biomarkers. CRO significantly decreased intracellular Ca2+ concentration and increased mitochondria membrane potential in H9c2 cells. CRO also resisted the DOX-induced high expression of tumor necrosis factor-a and interleukin-6, inhibited apoptosis and improved the abnormal expression levels of Bcl-2, Bax and Caspase-3 proteins. CRO obviously restrained DOX-mediated high expression of toll-like receptor-2 (TLR-2) and nuclear factor kappa-B (NF-kappa B) in ventricular tissue. In brief, CRO distinctly restrained DOX-mediated cardiotoxicity by inhibiting oxidative stress, inflammation, apoptotic and redressing cardiomyocyte calcium dyshomeostasis and mitochondria damage. These cardioprotective effects may be related closely with the TLR2/NF-kappa B pathway.