Objective: To evaluate the hypolipidemic and antioxidant effects of aqueous extract leaves of Anvillea radiata (AEL of A. radiata) in normal and streptozotocin (STZ) induced diabetic rats. In addition, the determination of total polyphenol and total flavonoid contents in the AEL of A. radiate was performed. Methods: The effects of oral administration of AEL of A. Radiata (10 mg/kg) on the plasma total cholesterol (TC), triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-C) concentrations were measured in both normal and diabetic rats. The antioxidant capacity was realized by the method of DPPH. Total polyphenol, as well as, flavonoid contents of the AEL of A. radiata were determined by Folin-Ciocalteu method and colorimetric AlCl3 method, respectively. Results: AEL of A. radiate (10 mg/kg) showed a strong hypolipidemic effect both in normoglycaemic and in STZ rats after 15 days of daily treatment. In normal rats, AEL of A. radiata induced a significant decrease in plasma triglyceride levels (p<0.0001). Moreover, plasma cholesterol total levels reduced significantly (p<0.05; p<0.0001) both in normal and diabetic rats, respectively. In contrast, plasma HDL-C levels showed a significant increase (p<0.05; p<0.01) both in normal and in STZ induced diabetic rats, respectively. On the other side, AEL of A. radiata showed important antioxidant activity and revealed the inhibitory concentration of 50% of free radicals (IC50) (IC50=343.41 mg/ml). Concerning the quantitative determination of total polyphenol and flavonoid contents, which were equal to 70.28 mg of gallic acid equivalent per gram of extract (mg EAG/g) and 16.38 mg of quercetin equivalent per gram of extract (EQ/g), respectively. Conclusion: AEL of A. radiata (10 mg/kg) shows the potential hypolipidemic and antioxidant effects in both normal and STZ-induced diabetic rats. Keywords: A. radiata, streptozotocin, total cholesterol, triglycerides, flavonoids, anti-oxidants.
Background: Arsenic is a naturally occurring contaminant in water. Its chronic exposure has been linked to several health problems, including cancer. Children are most affected by their exposure due to physiological conditions and certain nutrients, known to decrease the toxicity of the metalloid. Objective: The main objective was to analyze the food intake and nutritional status in children exposure to arsenic in water. Methods: A transversal study was conducted on cases of a historical cohort comprising forty three children, from two communities, Guanajuato, Mexico. The children were selected from the previous study, where they had 0.01 to 5.9 mg /kg of arsenic in hair (in both communities). The anthropometric variables included weight and height determined through BMI. Results: The average age was 11 ± 0.8 years old. Twenty-six percent of children were underweight and 19% were overweight and the correlation was negative between the arsenic levels reported in the previous study with the current BMI value (r= -0.5931; IC=- 0.1096-0.8361; p=0.0198). Only 26% had an adequate energy intake (1717±288kcal). The consumption of protein, folic acid, zinc and fiber was low according to RDA. The children used to have mainly soda, fried foods and processed foods. The water source was mainly bottled water in 58.1% of children´s families. The average consumption of milk was 250ml and its source was cow stables in 49%, with a significant difference between the two communities, regarding the origin of milk and water. Conclusion: The dietary intake was poor in quality and quantity with low intake in vitamins and micronutrients that are important for metabolism and lower toxicity of arsenic. The correlation between BMI and arsenic levels should be studied, since poor diet and poor nutritional status could exacerbate the complications of the metalloid. Keywords: Arsenic, children, eating, nutritional status, micronutrients, dietary intake.
Background: In present decades, interest in tetrazole chemistry has been increasing rapidly because of its broad range of biological applications, primarily due to the role played by tetrazole in medicinal chemistry as this moiety offer a more complimentary pharmacokinetic profile and a metabolically stable substitute for carboxylic acid functionalities. The heterocyclic tetrazole moiety has admirable biological, pharmaceutical and clinical applications. Method: There are various approaches available for the synthesis of tetrazole derivatives which are reported in the present survey. The most versatile method for the synthesis of tetrazoles is [2+3] cycloaddition reaction between nitriles and azides. Observations: Among the family of nitrogen-containing heterocycles, tetrazole and its derivatives exhibit a large range of biological properties such as antibacterial, antifungal, anticancer, analgesic, anti-inflammatory, antidiabetic, anti-hyperlipidemic and antitubercular activities. The unique features of tetrazole, biological significance and applications are discussed in this review. Conclusion: The present investigation reviews the various synthetic approaches and different biological activity of substituted tetrazole derivatives. The rationale of this review was to pool literature work reported by researchers on tetrazole for their various biological activities and also reported current efforts made on tetrazole moiety. Keywords: Tetrazole, synthesis, anti-inflammatory, anti-diabetic, anticancer, antibacterial activity.
Background and Aims: To our knowledge, no study has investigated neither how Moringa leaf extract modulates the immune system in normal nor diabetic subjects. Materials and Methods: Diabetes was induced by a single intraperitoneal dose of alloxan (150 mg/kg). A dose of 100 mg/kg of MO extract was orally administered to diabetic treated mice. The profile of glucose and insulin was evaluated. The activity of superoxide dismutase, catalase, glutathione peroxidase, and glutathione enzymes was determined. Liver function was monitored by measuring levels of alkaline phosphatase, glutamine pyruvate transaminase, and glutamic oxaloacetic transaminase. The percentage of single-or double-positive cells of each of CD8+/CD4+, CD117+/Sca-1+, Sca-1+/CD34+, CD11b+/Ly6-G+, CD11c+/CD11b+, and CD34+/CD117+ was investigated by flow cytometry in the peripheral blood. Results: MO promotes the activity of both CD4+ and CD8+ T cells in diabetic treated mice that may occur through the Sca-1+CD117+ stem cell factors. Administration of MO leaf extract enhanced the percentage of the endothelial progenitors (CD34+CD117+) and mature endothelial cells (CD34+CD117-). Moringa also increased the percentage of blood-derived circulating angiogenic cells (Sca-1+/CD34+). Discussion and Conclusions: This study shed light for the first time on how MO affects different immune cells; the knowledge gained may help to overcome diabetes and its complications. Keywords: CD8+CD4+ T cells, lipid peroxidation, circulating angiogenic cells, immune modulation, Moringa leaf, diabetes.
Background: Despite its key role in the treatment, major abdominal surgery has been indicated as a cause of a metabolic, neuroendocrine and immunological response. Several studies have demonstrated that the magnitude of this postoperative Systemic Inflammatory Response (SIR) is directly associated with the development of complications after colorectal surgery. Objective: The aim of the present study was to investigate the association between preoperative administration of corticosteroids and overall survival, disease free survival rates and anastomotic leakage in colorectal cancer patients treated with surgery. Methods: A retrospective review of prospectively collected data was performed of 354 patients with colorectal cancer who had undergone curative resection between June 2012 and December 2016, at the Surgical Oncology Unit, University Hospital of Messina. Results: A total of 249 patients matched the inclusion criteria and were included in this study. A total of 159 patients in stages I and II with negative lymph vascular invasion were included in the 'N- group' while 90 patients from stage III with positive lymph vascular invasion were included in 'N+ group'. The OS and DFS in N+ group showed a better 5-years OS (88,46% vs. 81,25%) and DFS (73% vs. 78,1%) rates for patients who have been given preoperative corticosteroids, but the Log-Rank test did not reach statistical significance. Also in the N- group, the Kaplan-Meier curves showed better 5-years OS (97% vs. 87,4%) and DFS (91,4% vs. 88,7%) rates for patients who have been given preoperative corticosteroids, but the Log-Rank test did not reach statistical significance. Moreover, the preoperative administration of corticosteroids did not modify the frequency of anastomotic leakage. Conclusion: This study has demonstrated that preoperative corticosteroids administration improves outcomes following colorectal surgery probably as a result of attenuating the SIR. Our results thus do not support avoiding low-dose preoperative corticosteroids in colorectal surgery. Nevertheless, further work is warranted to validate the influence of preoperative corticosteroids in colorectal surgery. Keywords: Pre-operative corticosteroids, colorectal surgery, oncological outcomes, neuroendocrine, anastomotic leakage, cancer.
Background: The metabolic syndrome unites three pathologies of the person – obesity, arterial hypertension and diabetes. In recent years the progressing of such distribution covering from 2.5% to 3.8% of the population with increase twice each 10-15 years is noted. Even at maintenance of level of sugar at diabetes accumulation of the secondary metabolites breaking small vessels isn't excluded. At the same time many life-endangering complications develop. Objective: To identify the possibilities of plasmapheresis in the prevention and treatment of complications of metabolic syndrome. Method: Analysis of the world literature data on complications of metabolic syndrome and methods of their treatment. Results: At metabolic syndrome the frequency of strokes and myocardial infarctions there is twice more often than in population. For 5-9 years the general life expectancy decreases. Disorders of microcirculation at diabetes lead to a retinopathy with total loss of sight, a nephropathy from the outcome in a renal failure, to polyneuropathy and diabetic foot syndrome with high risk of high level amputations of the lower extremities. At the same time medicamentous therapy is not able to prevent such complications and almost only way of removal of these pathological metabolites is therapeutic apheresis, mainly the plasmapheresis. Data from our own studies confirm the effectiveness of such tactics. Conclusion: Plasmapheresis has to be applied not only to the correction of already critical conditions, but also to their prevention.
Background: Now-a-days, discovery of bioactive compounds of plant origin is playing very important role in treatment of various ailments without any side effect world widely. Since, time immemorial, plants have been utilized as a source of Traditional System of Medicine and in India, one of the well known system is Ayurvedic System of Medicine that has been flourishing since thousands years for treatment of allergy, asthma and other inflammatory diseases. Objectives: To inhibit leukotrienes by a purified fraction of Ocimum tenuiflorum in HL- 60 cell lines. To investigate anti-inflammatory activities of a purified Fraction of Ocimum tenuiflorum in an OVA induced asthma model in BALB/c mice. Methods: Plant materials of Ocimum tenuiflorum whole plants were collected after identification and authentication from Vidisha, (M.P.), India and were shade dried, pulverized to powder and extracted after de-fatting in MEOH and DCM and then tested for LTC4, LTA4 and COX-2 inhibitory activities in HL-60 Cell lines. RTPCR was performed to determine the LTC4-synthase mRNA expression. The bio-active purified fraction PM-OT was then tested in vivo in an OVA-induced asthma model in BALB/c mice and inhibition of inflammation was assessed via in vivo imaging tomography. Results: The PM-OT inhibited activities of LTC4 by 52%, LTA4 by 25% and COX-2 by 99% in HL-60 cells and LTC4-synthase mRNA expression in HL-60 Cells. Intra-gastric administration of PM-OT at 100mg/kg body weight along with HPMC led to a reduction in an OVA-induced lung inflammation in asthma model in BALB/c mice. Conclusion: A purified PM-OT fraction showed significant anti-inflammatory activities both in vitro and in vivo, which supported its traditional use in the treatment of inflammatory lung disease and asthma. Keywords: Asthma, Ayurveda, holy basil, leukotriene-C4-synthase, leuktotriene-A4-hydrolase, cyclooxygenase-2, inflammation, in vivo imaging.
Background: This research was performed to investigate the effects of prostaglandins on the sexual functions of albino male rats. The effects of prostaglandins on LH, FSH, testosterone secretion and semen quality of the male rats were investigated. PGE1 induced a significant decline in the level of LH, FSH and testosterone levels. PGE1 also induced significant decline in the testis, epididymal and seminal vesicle weights. Conclusion: Furthermore, PGE1 caused significant reduction in sperm count, and significant decline in the viable and malformed sperm percent. However, PGF2α did not affect these parameters. Keywords: Reproduction, PGE1 , PGF2α, male, rats, LH, FSH, testosterone.
Objective: Pathogen microorganisms use pathogen-encoded factors resembling host factors to elude the host's immune system. Based on molecular mimicry, a hypothesis was developed based on the bioinformatics analysis which represents the microorganism’s interference with chicken MHC regulatory factors. Method: The sequences of chicken NLRC5 and CIITA were retrieved from NCBI and ensemble database; so that the regulatory factors were predicted by using STRING tools. Also, Swiss model tools were used to predict the 3D structure of these molecules. The Cluspro 2.0 tool was used inorder to reveal the intramolecular interaction. Moreover, to find out the sequence and structure similarity with microorganism, UniPortKB, VAST and 3D Match tools were used as the experimental instruments. Result: In summary, Roseomonas cervicalis, Acetobacter aceti, Azospirillum sp CAG239, Roseomonas cervicalis, Rickettsiales_bacterium, Lactobacillus_hilgardii, Lactobacillus sakei, Aciduliprofundum boonei, Geoglobus_acetivorans, Pyrococcus horikoshii, Corynebacterium accolens, Hydrocarboniphaga effusa, Rhodopirellula europaea, Protochlamydia amoebophila and Escherichia coli have the protein subunit with detectable similarity with MHC regulatory factors. Conclusion: Bioinformatics analysis discovered mimicry as the new aspect of immune evasion or immune suppression effects of microbial organism in addition to the molecular similarities in MHC regulatory factors which were revealed between mammals and birds. Keywords: Bacteria, bioinformatics, chicken, MHC, regulatory factors, immune system.
Background: Lactoferrin is a multifunctional protein found in breast milk. We previously reported the anti-obesity effects of enteric-coated lactoferrin (eLF). Objective: As the previous study included some subjects with high Body Mass Index (BMI) or low-Density Lipoprotein cholesterol (LDL-Cho), we investigated the antiobesity effect of lactoferrin excluding those subjects. Method: We conducted a subgroup analysis of a previous report excluding subjects with BMI ≥ 30 and/or hyper-LDL cholesterolemia. Results: Of the total 26 subjects in the previous study, 7 in the eLF group and 6 in the placebo group match the above criteria. The subgroup analysis revealed a significant decrease in visceral fat in the eLF group at week 8 compared with that at week 0 (-10.2 cm2, P < 0.01); no differences were observed in the placebo group. The mean visceral fat was also lower in the eLF group at week 8 compared with the placebo group (-16.2 cm2, P < 0.01). A significant decrease in BMI was observed in the eLF group at week 8 (-0.38 kg/m2, P < 0.05) compared with that at week 0. No differences were observed in the placebo group. The mean BMI was also lower in the eLF group at week 8 compared with that in the placebo group (-0.60 kg/m2, P < 0.05). Conclusion: eLF reduced visceral fat and BMI excluding subjects with obese and/or hyper- LDL cholesterolemia. Keywords: Lactoferrin, enteric-coated, visceral fat, BMI, RCT trial, subgroup analysis.
Background: Chronic and non-communicable diseases such as non-alcoholic fatty liver diseases, non-alcoholic steatohepatitis, obesity, diabetes, cardiovascular dysfunctions, renal insufficiency, alcoholism and other inflammation disorders often lead to severe organ damage. Fibrosis, on the contrary, is a complex phenomenon that may turn into critical conditions if not treated properly. Several biochemical pathways and signaling molecules, for instance, TGF-β, ECM, MMPs, Collagens, MAPK, AP-1, SMAD and NF-κB are responsible for the pathophysiology. In addition to these, inflammatory and pro-inflammatory cytokines are also blamed to be responsible in catalyzing fibrogenesis. Methods: The information was basically searched using PubMed, Google Scholar and Science Direct and put all together to correlate fibrosis pathophysiology. Only recent publications were targeted to show protective roles of Resveratrol in animal studies and human subjects. Findings: There is no effective treatment tactic available for curing fibrosis since multiple factors are associated with its progression; hence, it remains a big question to be answered by current healthcare associates. However, cell-based therapies have been showing quite effective approaches and are being suggested to counter fibrotic conditions. It is, however, highly expensive and complicated procedure and unfortunately, the availability of the strategy is limited worldwide. On the other hand, Resveratrol, a naturally occurring polyphenol which is largely being investigated in various animal models, cell cultures and human trials and thereby found highly potential in preventing measure against fibrosis. Conclusion: Our current study, therefore, tries to establish some molecular pathways which are responsible for the progression of pro-fibrogenesis and fibrosis. Our findings would also explore the possible inhibitory role of Resveratrol alongside fibrosis. Keywords: Fibrosis, TGF-β, collagens, MAPK, NF-κB, Resveratrol.
Background: Homeostasis of blood glucose concentration is a physiological phenomenon that is tightly regulated in humans and acts as a major cellular mechanism that decreases blood glucose during insulin-stimulated glucose transport. GLUT4 assumes a significant role in managing entire body glucose homeostasis. Recent research has found that overexpression of GLUT4 reduces glucose intolerance and diabetes. Interestingly, reduction of GLUT4 by inhibiting glucose transport has been found to have a powerful chemotherapeutic impact on myeloma. In order to further examine such interactions, a high-resolution crystal structure would be particularly useful. A homology model was produced for GLUT4 to screen for drug-like compounds and other docking complex connections. Conclusion: Our study provides further data for determining the role of GLUT controllers used to target glucose transport. Clarification of the three-dimensional structure of these transporters utilizing the steady, powerful and highly precise SWISS-MODEL protein structure prediction server will fundamentally help in the advancement of novel medications. The predicted model protein, GLUT4, demonstrated a comparable affinity for ATP and with inhibitor metformin binding motifs. Keywords: GLUT4, SWISS-MODEL, docking, ATP, metformin, homeostasis.
Background: Diabetic foot ulcer is a common disorder involving diabetic patients. Appling new indicators of the severity of diabetic foot infection may help the practitioners to develop more efficient diagnosis and treatment strategies. Methods: In this study, 70 diabetic patients with a foot ulcer, admitted to the infectious diseases ward of Tabriz education and treatment center between 2015 and 2016, were enrolled. The severity of infection was determined according to the Infectious Diseases Society of America clinical practice guideline. Twenty of these patients were excluded and further examinations were performed on 50 patients. On the first day of hospitalization and before antibiotic therapy, Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), Procalcitonin (PCT), White blood cells (WBCs), Fasting blood sugar (FBS) and HbA1C were measured. The level of these factors was then compared across four severity groups. Results: Pulse rate, respiratory rate, body temperature and leukocyte count were significantly higher in the patients with severe infection. ESR and CRP were higher in patients with more severe infection, but PCT and HbA1C level were not in accordance with the infection’s severity. Conclusion: In conclusion, ESR and CRP level can be more successfully used to discriminate patients, according to the severity of the infection. Keywords: Diabetic foot ulcer, biomarker, procalcitonin, infection, CRP, HbA1C.
Background: Programmed death-1 ligand 1 (PD-L1) is one of the most important immunoregulatory molecules expressed on the cell surface of many cell types under a variety of physiological and pathological conditions. One of its key functions is the inhibition of T cell effector activities by binding with programmed death-1 (PD-1) expressed on the surface of activated T and B cells. After its binding, PD-1 inhibits signal transduction of the T cell and B cell receptors. This immunosuppressive mechanism is widely used by many tumors to escape the immune attack, thereby favoring tumor progression. The systemic administration of antibodies that block PD-L1/PD-1 interactions to cancer patients is demonstrating unprecedented clinical success. This efficacy is usually explained by the reactivation of tumor-infiltrating T cells that have been inactivated by PD-L1/PD-1 interactions. However, PD-L1 also transmits intracellular signals to cancer cells that favour their survival. This intrinsic intracellular signaling may significantly contribute to tumor growth by conferring cancer cells resistance to apoptotic stimuli including interferons. Conclusion: Here we review the current knowledge on PD-L1 signal transduction in cancer cells and its role in tumor progression and resistance to anti-cancer therapies. Keywords: PD-L1, PDL1, B7-H1, CD274, immune checkpoint inhibitors, cancer immunotherapy, interferon, apoptosis.
Objectives: The angiotensin converting enzyme 2 (ACE2)/angiotensin-(1- 7)/Mas pathway has been expected to act as a protective arm of the renin-angiotensin system. Recently, the role of ACE2 in glucose metabolism has been highlighted. We previously reported that olmesartan increases ACE2 expression in injured arteries. Therefore, we hypothesized that treatment with olmesartan would improve glucose metabolism via ACE2 activation. Here, we investigated the effect of olmesartan on glucose metabolism using ACE2-deficient mice (ACE2KO). Methods: Ten-week-old WT and ACE2-deficient mice (ACE2KO) were employed in this study. Olmesartan or valsartan was administered intraperitoneally at a dose of 1.5 mg/kg/day in 8 weeks old mice. Insulin resistance was evaluated by oral glucose tolerance test and insulin tolerance test. Morphological changes in adipose tissue as well as adipocyte differentiation and inflammatory response and histological changes in the pancreas were examined. Results: ACE2KO showed significantly higher fasting blood glucose level and blood glucose level at 30 min after glucose load in the oral glucose tolerance test. Treatment with olmesartan reduced blood glucose level at 30 min after glucose load in both WT and ACE2KO, but valsartan did not. Treatment with olmesartan increased adipocyte number and reduced mean adipocyte size only in WT, but not in ACEKO. Treatment with olmesartan also prevented the reduced size of pancreatic islets in ACE2KO. Conclusion: The present study demonstrated that ACE2KO exhibited abnormal glucose metabolism. Treatment with olmesartan improved glucose metabolism in WT more than in ACEKO mice, indicating the possible existence of an ACE2-dependent pathway induced by olmesartan. Keywords: ACE2, olmesartan, glucose metabolism, pancreas, glucose tolerance, adipocyte.
Introduction: Withdrawal period from abused substance is accompanied by many problems. In some addicted people, relapse to drug-seeking and compulsive abuse develops. On time intervention may reduce relapse in some addicted people by knowing underlying mechanism. Methods and Materials: In this study 48 rats were randomly divided into four groups: pair, isolation, withdrawal pair, and withdrawal isolated. Rats in withdrawal groups after one week for acclimatization were first induced for morphine addiction by injection of increasing dose of morphine (5 mg/kg/rat in the first day to the final dose of 35 mg/kg/rat) for 7 days and then were withdrawn from morphine by the injection of naltrexone (3 mg/kg/rat) in 8 days. In control groups no treatment was applied. On day 14, rats in all groups were first evaluated for avoidance memory and novelty-seeking behavior. Then rats in day 15 were sacrificed and brain immediately removed for the assessment of oxidative stress (OS) status in the hippocampus and prefrontal cortex for malondialdehyde (MDA), glutathione and nitrite/nitrate. Results: Avoidance memory was better in withdrawal pair rats. Novelty-seeking behavior was increased in withdrawal isolated rats. Anxiety was reduced in withdrawal isolated rats. MDA was higher in withdrawal isolated rats. Glutathione and nitrite/nitrate were higher in withdrawal isolated rats. Conclusion: Pair state (socialization) improves avoidance memory, increases anxiety and reduces novelty-seeking behavior in withdrawal period. Also, oxidative stress markers responded differently to withdrawal stress in isolated and pair rats. Keywords: Avoidance memory and anxiety, glutathione, MDA, nitrite/nitrate, novelty-seeking behavior, prefrontal, hippocampus.
BACKGROUND:Insulin resistance is a frequent metabolic disorder in Polycystic Ovary Syndrome (PCOS). Moringa oleifera has been shown to increase insulin expres-sion and decrease the degree of insulin in diabetes mellitus, therefore it is expected that Moringa oleifera could decrease insulin levels and increase folliculogenesis in PCOS.OBJECTIVE:To prove the effect of Moringa oleifera leaf extract in various doses might decrease the insulin levels and increase folliculogenesis in female PCOS-insulin resistant rats.METHODS:The three month old white rat of Wistar strain (Rattus norvegicus) 100-130 grams were divided into five groups (n=8) including normal control, PCOS-insulin re-sistance, PCOS-insulin resistance given metformin and PCOS-resistance insulin were giv-en Moringa oleifera leaf extract in two doses. Then, the PCOS model-insulin resistance by injection of testosterone propionate for 28 days. After 14 days treatment, we analysed insulin levels and folliculogenesis.RESULTS:The PCOS control group showed a significant increase in insulin levels compared to the normal control group. The insulin levels from group treatment with Moringa oleifera leaf extract of 250 mg/kgBW was significantly lower than the PCOS control group. Ovarian histology analysis found that the number and diameter of follicle of PCOS control group showed a significant decrease compared to normal control group. In addition, the treatment with metformin and leaf Moringa oleifera dose 250 mg/kgBW and 500 mg/kgBW showed significant increase of folliculogenesis compared to PCOS control group.CONCLUSIONS:Moringa oleifera could lowering the blood insulin levels, subsequently decreasing the androgen thus allowed the increasing of folliculogenesis in PCOS.
Background: The immortalized human epidermal keratinocytes HaCaT often serve as an experimental model of psoriasis. Previously, we reported that Th1 cytokines TNF, IFN-γ and IL17 suppressed proliferation in cultured HaCaT cells. Our results also suggested that at certain conditions, HaCaT cells could become susceptible to the named cytokines. Objective: The aim of this study was to analyze the consequences of FOSL1 silencing in HaCaT cells and explore the role of the transcription factor FOSL1 in the above mentioned antiproliferative effect. Methods: Lentiviral transduction was used to knock FOSL1 down in HaCaT cells. Changes in cell proliferation were assessed by analyzing the growth of transduced cells. Changes in gene expression were examined by qPCR. Results: We found that the treatment of FOSL1-deficient HaCaT cells with a combination of TNF, IFN-γ and IL17 led to growth arrest and apoptosis. In turn, exposure of these cells to the individual cytokines suggested that the presence of IFN-γ in the culture medium was the primary cause of cell death. FOSL1-deficient cells exposed to IFN-γ exhibited a dramatic shape change and intensive blebbing. Moreover, TNF and IL17 accelerated IFN-γ- induced apoptosis. A comparative analysis of gene expression in control and FOSL1- deficient HaCaT cells discovered that only TNF induced ten FOSL1 target genes previously implicated in the pathogenesis of psoriasis, namely CCL2, FOSL1, HMOX1, IL8, IL6, IVL, MGP, MMP1, MMP9, and PLAUR. In contrast, neither IFN-γ nor IL17 produced similar changes in the expression profiles of the mentioned genes. Conclusion: The obtained results suggest that the transcription factor FOSL1 protects HaCaT cells from apoptosis triggered by IFN-γ. This study also reveals distinct roles of Th1 cytokines in the regulation of FOSL1 target genes. Keywords: Apoptosis, FOSL1, HaCaT, IFN-γ, IL17, psoriasis, TNF.
