Effects of bromodomain and extra-terminal inhibitor JQ1 and interleukin-6 on breast cancer cells.

BACKGROUND: Bromodomain and extra-terminal (BET) proteins are recognized acetylated lysine of histone 4 and act as scaffolds to recruit many other proteins to promoters and enhancers of active genes, especially at the super-enhancers of key genes, driving the transcription process and have been identified as potential therapeutic targets in breast cancer. However, the efficacy of BET inhibitors such as JQ1 in breast cancer therapy is impeded by interleukin-6 (IL-6) through an as-yet-defined mechanism. METHODS AND RESULTS: We investigated the interplay between IL-6 and JQ1 in MCF-7 and MDA-MB-231 human breast cancer cells. The results demonstrate that the efficacy of JQ1 on the inhibition of cell growth and apoptosis was stronger in MDA-MB-231 cells than in MCF-7 cells. Further, MCF-7 cells, but not MDA-MB-231 cells, exhibited increased expression of CXCR4 following IL-6 treatment. JQ1 significantly reduced CXCR4 surface expression in both cell lines and diminished the effects of IL-6 pre-treatment on MCF-7 cells. While IL-6 suppressed the extension of breast cancer stem cells in MCF-7 cells, JQ1 impeded its inhibitory effect. In MCF-7 cells JQ1 increased the number of senescent cells in a time-dependent manner. CONCLUSION: Analysis of gene expression indicated that JQ1 and IL-6 synergistically increase SNAIL expression and decrease c-MYC expression in MCF-7 cells. So, the BET proteins are promising, novel therapeutic targets in late-stage breast cancers. BET inhibitors similar to JQ1 show promise as therapeutic candidates for breast cancers, especially when triple-negative breast cancer cells are increased and/or tumor-promoting factors like IL-6 exist in the tumor microenvironment.

Molecular effects of genistein, as a potential anticancer agent, on CXCR-4 and VEGF pathway in acute lymphoblastic leukemia.

BACKGROUND: Vascular endothelial growth factor (VEGF) is one of the angiogenic mediators that can be secreted by leukemic cells and plays an important role in tumor invasion and metastasis. Another important agent contributing to the relapse of ALL is C-X-C chemokine receptor type-4 (CXCR-4), expression of this receptor in cancer cells has been related to metastasis. It has been identified that genistein-a soy-derived isoflavonoid-has anti-angiogenesis functions. We aimed to show the effects of this compound on VEGF and CXCR-4 in Acute lymphoblastic leukemia (ALL) cell models. METHODS AND RESULTS: The cytotoxicity of Genistein was measured using the MTS colorimetric assay. After being treated with Genistein, the expression of VEGF in mRNA and protein levels was measured in MOLT-4 and Jurkat cells. We also used flow cytometry assay to determine the expression of CXCR-4 in cell surfaces. We found that Genistein decreased cell viability in two cell models while was more effective on MOLT-4 cells. After Genistein-treatment, surface expression levels of CXCR-4 were decreased, while VEGF secretion and mRNA expression levels were increased in MOLT-4 and Jurkat cells. CONCLUSIONS: The results suggest that Genistein may not be a reliable choice for the treatment of ALL; however, this different identified pattern can be useful for the recognition of VEGF and CXCR-4 modulators and thus for planning new treatments for leukemia and other VEGF related disorders.

Correlation between aryl hydrocarbon receptor and IL-17+ and Foxp3+ T-cell infiltration in bladder cancer.

Bladder cancer (BC) is one of the most prevalent cancers around the world and, if not treated well, has high morbidity and mortality. Many studies have indicated that there may be various roles for the aryl hydrocarbon receptor (AHR) in the immune system. The aim of this study was to determine the frequency of Foxp3+ regulatory T (Treg) and T helper 17 cells (Th17) in BC tissue in comparison with controls and determine the relationship between AHR, Foxp3+ Treg and Th17 cells in BC. A total of 40 patients with BC were enrolled in this study. The control group was selected from non-tumoural parts of bladder tissues from the patients who have undergone cystoscopy. The percentage of regulatory T cells (Foxp3+ /CD4+ ) and Th17 (IL-17+ /CD4+ ), as well as AHR+ cells in BC tissues and controls, were determined by immunohistochemistry. The results of this study showed that the number of Foxp3+ Treg and Th17 is significantly higher in bladder tumour tissues in comparison with non-tumoural tissues. Also, the percentage of AHR+ lymphocytes and AHR+ cells was increased significantly in bladder tumour tissues rather than non-tumoural tissues. This study also found a relation between AHR and Foxp3+ /CD4+ T lymphocytes ratio cells in BC. The percentage of Foxp3+ Tregs and AHR+ cells were significantly correlated with the grade and stage of BC. An increase in the percentage of Foxp3+ Treg and Th17 cells may play an important role in tumour immunity; and determining the relationship between AHR and differentiation of Th17/Foxp3+ Treg in BC can lead to a potential cancer therapeutic possibility.

Comparing the frequency of CD33+ pSTAT3+ myeloid-derived suppressor cells and IL-17+ lymphocytes in patients with prostate cancer and benign prostatic hyperplasia.

Prostate cancer (PCa) is one of the most epidemic types of cancer in men. The tumor microenvironment (TME) of PCa is involved in the emergence of immunosuppressive factors such as myeloid-derived suppressor cells (MDSC), which regulate the immune system by several mechanisms, including interleukin (IL)-10 production. On the other hand, IL-17+ helper T cells (Th17) induce MDSCs and chronic inflammation in TME by producing IL-17. This study demonstrated that the frequency of CD33+ pSTAT3+ MDSC and IL-17+ lymphocyte as well as IL-10 messenger RNA (mRNA) expression were significantly higher in the PCa patients than in the benign prostatic hyperplasia (BPH) group. Moreover, there was no significant relationship between the frequency of CD33+ pSTAT3+ MDSC, and IL-17+ lymphocyte with Gleason scores in the PCa group. We suggested that the higher frequency of CD33+ pSTAT3+ MDSC and IL-17+ lymphocyte and the more frequent expression of IL-10 mRNA in PCa patients may play roles in tumor progression from BPH to PCa.

Local Expression of Mucosal YKL-40; Correlation of YKL-40 with Clinical Manifestations and Immunopathogenesis of Moderate/Severe Persistent Allergic Rhinitis Patients.

YKL-40 is an important protein that plays a critical role in chronic inflammation in hypersensitivity disease. In this study, the expression of YKL-40 was investigated among patients with moderate/severe persistent allergic rhinitis (M/S PAR), patients with mild (M) PAR and healthy individuals. Moreover, the association between YKL-40 and immunopathogenesis of M/S PAR was meticulously surveyed. For this purpose, surgical samples were tested by real-time polymerase chain reaction to evaluate YKL-40 mRNA expression. The presence and location of YKL-40 protein in the tissue samples were determined by immunohistochemistry. Additionally, we measured the number of eosinophils per field in the tissue samples, blood eosinophils, total serum IgE, specific serum IgE, total nasal syndrome score (TNSS) and YKL-40 serum levels. The data indicated that production of YKL-40 in patients with M/S PAR increased significantly when compared with the control group. Furthermore, local production of YKL-40 correlated with specific IgE, nasal eosinophil count and TNSS. The results of the present study indicate that YKL-40, for its correlation with allergic clinical manifestations and symptom severity in M/S PAR patients, should be considered as a trigger factor in AR.

The protective effects of resveratrol on ulcerative colitis via changing the profile of Nrf2 and IL-1ß protein.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) with increasing incidence and prevalence in developed countries. The presence of inflammatory cytokines is considered the main detrimental factor in severe types of IBD. The Nrf2 transcription factor plays an important role in reducing the expression of inflammatory agents such as interleukin (IL)-1ß and increasing reparative factors such as IL-11. Resveratrol, a plant-derived phenolic compound, reduces the damage in chronic experimentally induced colitis. Twenty patients with UC and also 20 healthy controls were recruited in this study. The proteins expression of Nrf2 and IL-1ß was assessed in colonic biopsies by Western blotting. Caco-2 cells were challenged with TNF-α (in vitro simulation of UC), in the presence or not of 190 nM (24 h) and 75 nM (48 h) Resveratrol. Then, Nrf2 and IL-1ß in gene and protein expression were measured by real time-PCR and Western blotting in different treatments. Finally, IL-11 proteins expression was measured in culture supernatant by ELISA. A significant increase of IL-1ß protein was detected in inflamed colonic tissues from UC patients compared with the control individuals. In Caco-2 cells challenged with TNF-α, protein expression of IL-1ß and p-Nrf2 showed an increase, while gene expression of Nrf2 did not show a significant difference. After treatment with Resveratrol, both IL-1ß mRNA and protein levels were reduced, while IL-11 protein levels showed any increase. The p-Nrf2 is a dominant form which is prevalent in inflamed tissues from UC patients. Resveratrol can reverse the inflammatory effects of TNF-α by reducing IL-1ß and increasing IL-11 production.

Role of Th22 cells in Helicobacter pylori-related gastritis and peptic ulcer diseases.

Helicobacter pylori (H. pylori) has been shown to be one of the leading causes of peptic ulcer diseases (PUDs) and gastritis. T helper-22 (Th22) cells and its most important cytokine, interleukin-22 (IL-22) are importantly active in inflammation and inflammatory tissues. Since inflammation is one of the main attributes of infection caused by H. pylori and resulting complications (gastritis and gastrointestinal ulcer), this study was designed to evaluate the Th22 cells count and the IL-22 protein expression in people suffering from PUD and gastritis. The present study was conducted on 55 patients with gastritis, 47 patients with PUD and 48 uninfected subjects. After preparation of section and extraction of protein from antral biopsies, immunohistochemistry and western blot methods were used to evaluate the Th22 cells and IL-22 protein expression level, respectively. According to findings, the Th22 cells count and the IL-22 protein expression level in the infected subjects were siginficantly more than in the uninfected subjects. It should be noted that the Th22 cells count and the IL-22 protein expression level in the infected subjects with PUD were significantly greater than those in the infected subjects with gastritis. In addition, the Th22 cells count had positive correlation with the density of H. pylori, chronic inflammation score and acute inflammatory score in the infected subjects with PUD. The Th22 cells count had positive correlation with the Th17 cells count and inverse correlation with the Treg cells count in the infected subjects with PUD and gastritis. Our data demonstrated that abnormal hyper-activation of Th22 cells as well as its correlation with the Th17 cells during infection caused by H. pylori might damage tissues through immunopathological responses.

The relationship between IL-17A and IL-22 expression and clinical severity in patients with moderate/severe persistent allergic rhinitis.

PURPOSE: Several reactions leading to numerous effects are regulated by IL-22. However, the relationship between IL-22 and immunopathogensis of allergic rhinitis (AR) has been rarely investigated. The aim of the present study was to investigate the levels of IL-22 and IL-17A in AR patients and their association with clinical severity of persistent allergic rhinitis (PAR). MATERIALS AND METHODS: Thirty mild persistent allergic rhinitis (M PAR) patients, thirty moderate/severe persistent allergic rhinitis (M/S PAR) patients, and thirty healthy controls were enrolled in this study. Local production of IL-22 and IL-17A in PAR patients and healthy controls' nasal mucosa was examined by immunohistochemistry (IHC) and real-time polymerase chain reaction (RT-PCR) techniques. Serum levels of IL-22, IL-17A, specific immunoglobulin E (sIgE), and total IgE (tIgE) in PAR patients and healthy controls were determined by ELISA. In addition, blood eosinophil, nasal eosinophils per field, and total nasal syndrome score (TNSS) were also assessed. RESULTS: In comparison with healthy controls, production of IL-22 and IL-17A in M/S PAR patients increased significantly. Furthermore, serum levels as well as the mean number of IL-22+ and IL-17A+ cells in nasal mucosa correlated with sIgE, nasal eosinophil count, and TNSS. CONCLUSION: The results of the present study provide the first evidence that local production of IL-22 might be expressed in PAR patients. The expression of IL-22 and IL-17A, and their correlations with clinical parameters in PAR patients suggest the role of these cytokines in the events involved in the development of PAR.

The expression analysis of Fra-1 gene and IL-11 protein in Iranian patients with ulcerative colitis.

BACKGROUND: Fra-1 (fosl1) belongs to the activator protein1 (AP-1) family inducing IL-11 expression in oxidative stress condition. IL-11 plays a pivotal role in protecting epithelial barriers integrity. In this study, we investigated the Fra-1 gene expression in the inflamed mucosa of patients with ulcerative colitis (UC) as well as its relation to IL-11 expression. MATERIALS AND METHODS: We enrolled 20 patients and 20 healthy controls with definite UC based on the clinical criteria. Fra-1 gene expression in inflamed and non-inflamed colonic biopsies was determined by real-time polymerase chain reaction (RT-PCR). The IL-11 protein concentration was measured by Enzyme-Linked Immunosorbent Assay (ELISA) method. Pearson correlation was applied to calculate the relation between Fra-1 and IL-11. RESULTS: An increased level of Fra-1 gene expression was observed in patients with mild ulcerative colitis. The protein concentration of IL-11 was also increased in mild UC patients. Conversely, a significant decrease of IL-11 protein level was detected in severe UC patients compared to control group. CONCLUSION: Oxidative stress in inflamed intestinal biopsies can induce fra-1 gene expression. Our findings suggest that Fra-1 transcription factor leads to the production of IL-11 protein in UC patients.

The role of T helper 1-cell response in Helicobacter pylori-infection.

Helicobacter pylori (H. pylori) is a human pathogen affecting over 50% of the world population. This pathogen is usually associated with chronic inflammation of the gastric mucosa that can lead to peptic ulcer disease (PUD) and gastric cancer (GC), especially in susceptible individuals. These outcomes have been attributed to the interaction of several factors, including host genetic susceptibility, local innate and adaptive immune responses, virulence factors of H. pylori, and environmental factors. T helper (Th) cell subsets and their signature cytokines especially IFN-γ, contribute to anti-bacterial response, but at the mean time sustaining chronic inflammatory responses in the site of infection. It has been acknowledged that H. pylori-infection results in a Th1-dominant response and that inflammation of the gastric mucosa depends mainly on Th1 cell responses. But, the mechanism of the role of Th1 cell responses in H. pylori-infection has not yet been clearly explained. In this review, we will focus on the role of Th1 involved in H. pylori-infection, its interaction with Th17/Treg cells and its association with the clinical consequences of the infection.

Intensified Th9 Response is Associated with the Immunopathogenesis of Active Ulcerative Colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disorder of the large intestine histologically characterized by indistinct sustained inflammatory responses. Genetical susceptibility and environmental factors' effects play the roles in disease occurrence and it can be life threatening if remains untreated. It seems that intensification of inflammatory responses in this condition is not restricted to a specific cell line of T lymphocytes. Our aim was to determine the number of T helper 9 (Th9) cells in inflamed colonic biopsies of UC patients. We also correlated it with interleukin (IL)-9 protein level in addition to certain genes expressions associated with Th9 phenotype. METHODS: Expression of CD4 and IL-9 were evaluated by immunohistochemical staining. Enzyme linked immunosorbent assay (ELISA) was performed to determine the colonic expression of IL-9 protein and finally mRNA expressions of interferon regulatory factor 4 (Irf4), Smad2, and Smad3 were measured by real-time polymerase chain reaction (RT-PCR) as critical transcription factors of Th9 differentiation. RESULTS: Number of Th9 cells was significantly increased in inflamed samples as compared with normal tissues. Also quantitative measurement of IL-9 by ELISA and mRNA expressions of Irf4, Smad2, and Smad3 showed notable correlative enhancements in patient's samples. CONCLUSION: Function and number of Th9 cells are up-regulated in the inflamed mucosa of UC patients as with the protein secretion of IL-9 and mRNA expressions of Irf4, Smad2, and Smad3, so Th9 cells and IL-9 may become remarkable therapeutic targets for IBD treatment in the future.

Differential expression of CCL18 in moderate/severe and mild persistent allergic rhinitis and its correlation with disease parameters.

BACKGROUND AND AIMS: This study aimed to assess the level of the expression of CCL-18 on nasal inferior turbinate mucosa in patients with mild (M) and moderate-to-severe (M/S) persistent allergic rhinitis (PAR). METHODS: The participants in this case-controlled study were divided into three groups: patients with M/S PAR, patients with M PAR, and the healthy control group. Biopsies of nasal inferior turbinate mucosa were obtained from the participants. Expression of CCL-18 mRNA was evaluated by real-time PCR. The serum levels of CCL-18 were determined by ELISA. Total serum IgE levels and specific serum IgE levels were measured. The clinical manifestations were assessed using the total nasal syndrome score (TNSS). RESULTS: Gene expression and the serum level of CCL-18 in patients with M/S PAR increased significantly compared to the control group and patients with M PAR. The serum level of CCL-18 was found to correlate with TNSS in patients with M/S PAR. There was a statistical correlation between the serum level of CCL-18 and the total serum IgE in the treatment groups. CONCLUSION: The results of the study indicate that there could be a relationship between the expression of CCL-18 in nasal turbinate mucosa and the severity of allergic rhinitis.

In vitro immunomodulatory activity of celastrol against influenza A virus infection.

CONTEXT: The influenza A virus (IAV) causes severe respiratory disease that remains a leading reason for morbidity and mortality. Previous studies have indicated that influenza complications in addition to viral replication are due to overproduction of pro-inflammatory cytokines. Therefore, a new compound is needed to be used with current antiviral drugs to modulate overproduction of pro-inflammatory cytokines in IAV infection. OBJECTIVE: This study investigated the effect of celastrol on mRNA expression and concentration levels of the pro-inflammatory cytokines tumor necrosis factor alpha (TNFα) and interleukin-6 (IL6) that are induced by influenza A/Puerto Rico/8/34 (H1N1; PR8) in Madin-Darby Canine Kidney (MDCK) cells. The effect of this compound on virus titration and viral mRNA expression was also investigated. METHODS: Confluent MDCK cells were infected with influenza virus (H1N1; PR8) and treated with celastrol at different concentrations. After incubation, mRNA expression and concentrations of TNFα and IL6 were investigated using real-time polymerase chain reaction (PCR) and ELISA. The viral mRNA expression and virus titration were investigated using real-time PCR and 50% tissue culture infectious dose (TCID50) assay, respectively. RESULTS: mRNA expression and concentrations of TNFα and IL6 increased significantly in control virus compared to cell control, and decreased significantly when compared with control virus after celastrol treatment. Viral mRNA expression and virus titration did not decrease after celastrol treatment. CONCLUSION: Due to reducing mRNA expression and concentrations of TNFα and IL6, celastrol can serve as a suitable choice to control cytokine-induced inflammation in IAV infection, and therefore it can be used with current antiviral drugs.

Correlation of interleukin 6 and transforming growth factor ß1 with peripheral blood regulatory T cells in rheumatoid arthritis patients: a potential biomarker.

INTRODUCTION: Proinflammatory cytokines and regulatory T cells (Tregs) are considered as important factors involved in autoimmunity development especially in rheumatoid arthritis (RA). AIM OF THE STUDY: To investigate the frequency of peripheral blood Tregs and related cytokines in RA patients and to determine the possible correlation between Treg percentage and interleukin 6 (IL-6) and transforming growth factor ß1 (TGF-ß1) as indicators in assessment of Treg function and mechanisms preceding autoimmunity in RA. MATERIAL AND METHODS: Thirty-seven Iranian RA patients with a moderate (3.2-5.1) disease activity score (DAS) and the same number of healthy age- and sex-matched individuals were enrolled. Frequency of peripheral blood Tregs (CD4+FoxP3+CD25high) was determined by flow cytometry. Serum levels of IL-6 and TGF-ß1 and their expression levels in peripheral blood mononuclear cells (PBMCs) were evaluated by ELISA and Q-PCR, respectively. RESULTS: Rheumatoid arthritis patients showed significantly lower peripheral blood Treg frequencies compared to healthy individuals. Additionally, Treg (%) showed a significant inverse correlation between serum concentrations of IL-6 and mRNA expression of PBMCs, whereas there was no significant correlation between Treg (%) and TGF-ß1 levels. CONCLUSIONS: The current study revealed that Treg numbers were reduced in peripheral blood of RA patients. This reduction inversely correlated with IL-6 levels, which may lead to persistent autoimmune and inflammatory conditions in RA patients.

Downregulated regulatory T cell function is associated with increased peptic ulcer in Helicobacter pylori-infection.

BACKGROUND: Helicobacter pylori (H. pylori) chronically colonizes gastric/duodenal mucosa and induces gastroduodenal disease such as gastritis and peptic ulcer and induces vigorous innate and specific immune responses; however, the infection is not removed, a state of chronic active gastritis persists for life if untreated. The objective of this study was to determine the number of regulatory T cells (Tregs) in gastric mucosa of patients with gastritis and peptic ulcer and determined the relationship between main virulence factor of H. pylori and Tregs. METHODS AND MATERIALS: A total of 89 patients with gastritis, 63 patients with peptic ulcer and 40 healthy, H. pylori-negative subjects were enrolled in this study. Expression of CD4 and Foxp3 was determined by immunohistochemistry. Antrum biopsy was obtained for detection of H. pylori, bacterial virulence factors and histopathological assessments. TGF-ß1, IL-10 and FOXP3 expressions were determined by real-time polymerase chain reaction (qPCR). RESULTS: The numbers of CD4+ and Foxp3+ T cells as well as the expression of IL-10, TGF-ß1, FOXP3, INF-γ and IL-17A in infected patients were significantly higher than the ones in uninfected patients. Also, the number of CD4+ T cells was independent on the vacuolating cytotoxin A (vacA) and outer inflammatory protein A (oipA), but it was positively correlated with cytotoxin-associated gene A (cagA). Instead, the number of Foxp3+ T cells was dependent on the vacA and oipA, but it was independent on cagA. The number of Foxp3+ T cells and the expression of IL-10, TGF-ß1 and FOXP3 in infected patients with gastritis were significantly higher than the ones in infected patients with peptic ulcer. Moreover, the number of CD4+ T cells and the expression of IL-17A and INF-γ was the lowest in the gastritis patients, however, increased progressively in the peptic ulcer patients. Additionally, the numbers of CD4+ and Foxp3+ T cells as well as the expression of IL-10, TGF-ß1, FOXP3 and INF-γ were positively correlated with the degree of H. pylori density and chronic inflammation. CONCLUSION: Tregs are positively associated with vacA alleles and oipA status of H. pylori and histological grade but negatively associated with peptic ulcer disease.

Study of the tumor microenvironment during breast cancer progression.

BACKGROUND: Different cells and mediators in the tumor microenvironment play important roles in the progression of breast cancer. The aim of this study was to determine the composition of the microenvironment during tumor progression in order to discover new related biomarkers and potentials for targeted therapy. METHODS: In this study, breast cancer biopsies from four different stages, and control breast biopsies were collected. Then, the mRNA expression of several markers related to different CD4+ T cell subsets including regulatory T cells (Treg), T helper (Th) type 1, 2 and 17 were determined. In addition, we investigated the expression of two inflammatory cytokines (TNF-α and IL-6) and inflammatory mediators including FASL, IDO, SOCS1, VEGF, and CCR7. RESULTS: The results showed that the expression of Th1 and Th17 genes was decreased in tumor tissues compared to control tissues. In addition, we found that the gene expression related to these two cell subsets decreased during cancer progression. Moreover, the expression level of TNF-α increased with tumor progression. CONCLUSION: We conclude that the expression of genes related to immune response and inflammation is different between tumor tissues and control tissues. In addition, this difference was perpetuated through the different stages of cancer.

Production of stable GFP-expressing neural cells from P19 embryonal carcinoma stem cells.

Murine P19 embryonal carcinoma (EC) cells are convenient to differentiate into all germ layer derivatives. One of the advantages of P19 cells is that the exogenous DNA can be easily inserted into them. Here, at the first part of this study, we generated stable GFP-expressing P19 cells (P19-GFP+). FACS and western-blot analysis confirmed stable expression of GFP in the cells. We previously demonstrated the efficient induction of neuronal differentiation from mouse ES and EC cells by application of a neuroprotective drug, selegiline In the second part of this study selegiline was used to induce differentiation of P19-GFP+ into stable GFP-expressing neuron-like cells. Cresyl violet staining confirmed neuronal morphology of the differentiated cells. Furthermore, real-time PCR and immunoflourescence approved the expression of neuron specific markers. P19-GFP+ cells were able to survive, migrate and integrated into host tissues when transplanted to developing chick embryo CNS. The obtained live GFP-expressing cells can be used as an abundant source of developmentally pluripotent material for transplantation studies, investigating the cellular and molecular aspects of early differentiation.

Inhibition of Th1 and Th17 Cells by Medicinal Plants and Their Derivatives: A Systematic Review.

Searching for new natural drugs that are capable of targeting Th1 and Th17 may lead to development of more effective treatments for inflammatory and autoimmune diseases. Most of the natural drugs can be derived from plants that are used in traditional medicine and folk medicine. The aim of this systematic review is to identify and introduce plants or plant derivatives that are effective on inflammatory diseases by inhibiting Th1 and Th17 responses. To achieve this purpose, the search terms herb, herbal medicine, herbal drug, medicinal plant, phytochemical, traditional Chinese medicine, Ayurvedic medicine, natural compound, inflammation, inflammatory diseases, Th1, Th17, T helper 1 or T helper 17 were used separately in Title/Keywords/Abstract in Web of Science and PubMed databases. In articles investigating the effect of the medicinal plants and their derivatives in inhibiting Th1 and Th17 cells, the effects of eight extracts of the medicinal plants, 21 plant-based compounds and some of their derivatives, and eight drugs derived from the medicinal plants' compounds in inhibiting Th1 and Th17 cells were reviewed. The results showed that medicinal plants and their derivates are able to suppress Th17 and Th1 T cell functions as well as cytokine secretion and differentiation. The results can be used to produce herbal drugs that suppress Th, especially Th17, responses. Copyright © 2017 John Wiley & Sons, Ltd.

cag Pathogenicity island-dependent upregulation of matrix metalloproteinase-7 in infected patients with Helicobacter pylori.

Helicobacter pylori (H. pylori) infection has been involved in the pathogenesis of most important gastroduodenal diseases. Matrix metalloproteinases (MMPs) are a large family of zincendopeptidases which play important roles in degradation of extracellular matrix (ECM) and various inflammatory diseases. Therefore, we examined MMP-7 mRNA levels in the gastric mucosa of patients with H. pylori infection and evaluated the effects of virulence factors, such as vacA (vacuolating cytotoxin A) and cagA (cytotoxin-associated gene), in H. pylori-infected patients upon the MMP-7 mRNA mucosal levels. We also determined the correlation between mucosal MMP-7 mRNA levels and the types of disease. Total RNA was extracted from gastric biopsies of 50 H. pylori-infected patients and 50 uninfected individuals. Mucosal MMP-7 mRNA expression level in H. pylori-infected and non-infected gastric biopsies was determined by real-time polymerase chain reaction (PCR). The presences of cagA and vacA virulence factors was evaluated using PCR. MMP-7 expression was significantly higher in biopsies of patients infected with H .pylori compared to uninfected individuals. In addition, mucosal MMP-7 mRNA expression in H. pylori-infected patients significantly associated with the cagA status and the types of disease. Our results suggest that MMP-7 might be involved in the pathogenesis of H. pylori. Peptic ulcer was associated with cag pathogenicity island-dependent MMP-7 upregulation.