Regulation Of Chronic Inflammation Research Articles

Chito-oligosaccharides and macrophages have synergistic effects on improving ovarian stem cells function by regulating inflammatory factors

BackgroundChronic low-grade inflammation and ovarian germline stem cells (OGSCs) aging are important reasons for the decline of ovarian reserve function, resulting in ovarian aging and infertility. Regulation of chronic inflammation is expected to promote the proliferation and differentiation of OGSCs, which will become a key means for maintaining and remodeling ovarian function. Our previous study demonstrated that Chitosan Oligosaccharides (Cos) promoted the OGSCs proliferation and remodelled the ovarian function through improving the secretion of immune related factors,but the mechanism remains unclear, and the role of macrophages, the important source of various inflammatory mediators in the ovary needs to be further studied. In this study, we used the method of macrophages and OGSCs co-culture to observe the effect and mechanism of Cos on OGSCs, and explore what contribution macrophages give during this process. Our finding provides new drug treatment options and methods for the prevention and treatment of premature ovarian failure and infertility.MethodsWe used the method of macrophages and OGSCs co-culture to observe the effect and mechanism of Cos on OGSCs, and explore the important contribution of macrophages in it. The immunohistochemical staining was used to locate the OGSCs in the mouse ovary. Immunofluorescent staining, RT-qPCR and ALP staining were used to identify the OGSCs. CCK-8 and western blot were used to evaluate the OGSCs proliferation. β-galactosidase(SA-β-Gal) staining and western blot were used to detect the changing of cyclin-dependent kinase inhibitor 1A(P21), P53, Recombinant Sirtuin 1(SIRT1) and Recombinant Sirtuin 3(SIRT3). The levels of immune factors IL-2, IL-10, TNF-α and TGF-β were explored by using Western blot and ELISA.ResultsWe found that Cos promoted OGSCs proliferation in a dose-and time-dependent manner, accompanied by IL-2, TNF-α increase and IL-10, TGF-β decrease. Mouse monocyte-macrophages Leukemia cells(RAW) can also produce the same effect as Cos. When combined with Cos, it can enhance the proliferative effect of Cos in OGSCs, and further increase IL-2, TNF-α and further decrease IL-10, TGF-β. The macrophages can enhance the proliferative effect of Cos in OGSCs is also associated with the further increase in IL-2, TNF-α and the further decrease in IL-10, TGF-β. In this study, we determined that the anti-aging genes SIRT-1 and SIRT-3 protein levels were increased by Cos and RAW respectively, whereas the senescence-associated SA-β-Gal and aging genes P21 and P53 were decreased. Cos and RAW had a protective effect on OGSCs delaying aging. Furthermore, RAW can further decrease the SA-β-Gal and aging genes P21 and P53 by Cos, and further increase SIRT1 and SIRT3 protein levels in OGSCs by Cos.ConclusionIn conclusion, Cos and macrophages have synergistic effects on improving OGSCs function and delaying ovarian aging by regulating inflammatory factors.

Dietary Inflammatory Index and risk of breast cancer: evidence from a prospective cohort of 67,879 women followed for 20years in France.

Inflammation is implicated in breast cancer development, and diet is one of the modifiable risk factors involved in the regulation of chronic inflammation. Previous studies on the association between breast cancer risk and Dietary Inflammatory Indexes (DII) derived from food frequency questionnaires and data on inflammatory potential of dietary components have reported inconsistent results. To investigate the association between the DII and the risk of breast cancer using data from a large population-based cohort study. A total of 67,879 women from the E3N cohort were followed from 1993 to 2014. A total of 5686 breast cancer cases were diagnosed during the follow-up. The food frequency questionnaire administered at baseline in 1993 was used to calculate an adapted DII. Cox proportional hazard models using age as the time scale were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Spline regression was used to determine any dose-response relationship. We also evaluated effect modification by menopausal status, body mass index, smoking status and alcohol consumption. The median DII score of the study population was slightly pro-inflammatory (DII = + 0.39); ranged from -4.68 in the lowest quintile to + 4.29 in the highest quintile.The HR increased linearly with the DII (HR per 1SD = 1.04 [95% CI: 1.01, 1.07]), and reached 1.13 [95% CI: 1.04, 1.23] in the 5th quintile group as compared to the first. A positive linear dose-response relationship was also observed when modeling DII with spline functions. Slightly higher HRs were observed in non-smokers (HR for 1-SD increase 1.06 [95% CI: 1.02, 1.10]; p trend = 0.001) and in low-alcohol consumers (≤ 1 glass/day) (HR for 1-SD increase 1.05 [95% CI: 1.01, 1.08]; p trend = 0.002). Our results suggest a positive association between DII and breast cancer risk. Consequently, the promotion of anti-inflammatory diet may contribute to breast cancer prevention.

Role of interleukin‐35 in cardiovascular diseases

AbstractCardiovascular disease represents a complex series of clinical syndromes with multiple aetiologies. Cardiovascular diseases have become one of the most common causes of death among middle‐aged and elderly people worldwide because of their diverse types and wide range of patients. With the development of research in this field, increasing evidence shows that cytokines remain important to address in the beginning, progression and outcome of cardiovascular diseases. The interleukin (IL)‐12 family, which includes IL‐12, IL‐23, IL‐27 and IL‐35, is an important family of cytokines that plays roles in the regulation of chronic inflammation, tumour progression, autoimmune disease and cardiovascular disease. IL‐12 family members have distinct pro‐inflammatory and anti‐inflammatory effects and affect the progression of cardiovascular disease all the time. In particular, the novel member of this family IL‐35 has turned out to play a major part in the occurrence and development of various cardiovascular diseases such as atherosclerosis, acute coronary syndrome, myocardial infarction and viral myocarditis. In this review, the source, structure, receptor, signal transduction and biological functions of IL‐35 are summarized with a focus on the relationship with cardiovascular disease. We further discuss the molecular and cellular mechanisms that may be involved in these effects to guide the development of new strategies targeting IL‐35 for the prevention and clinical treatment of cardiovascular disease.

Volatile organic compounds: A proinflammatory activator in autoimmune diseases.

The etiopathogenesis of inflammatory and autoimmune diseases, including pulmonary disease, atherosclerosis, and rheumatoid arthritis, has been linked to human exposure to volatile organic compounds (VOC) present in the environment. Chronic inflammation due to immune breakdown and malfunctioning of the immune system has been projected to play a major role in the initiation and progression of autoimmune disorders. Macrophages, major phagocytes involved in the regulation of chronic inflammation, are a major target of VOC. Excessive and prolonged activation of immune cells (T and B lymphocytes) and overexpression of the master pro-inflammatory constituents [cytokine and tumor necrosis factor-alpha, together with other mediators (interleukin-6, interleukin-1, and interferon-gamma)] have been shown to play a central role in the pathogenesis of autoimmune inflammatory responses. The function and efficiency of the immune system resulting in immunostimulation and immunosuppression are a result of exogenous and endogenous factors. An autoimmune disorder is a by-product of the overproduction of these inflammatory mediators. Additionally, an excess of these toxicants helps in promoting autoimmunity through alterations in DNA methylation in CD4 T cells. The purpose of this review is to shed light on the possible role of VOC exposure in the onset and progression of autoimmune diseases.

Features of innate and adaptive immunity in patients with Parkinson's disease

Introduction. T cells play a significant role in neuroinflammation in Parkinson's disease (PD). Gamma delta T cells are an under-researched 'minor' subpopulation of T cells. An assessment of the immune system in patients with PD, with a focus on Т cells, provides new data on the pathogenesis of neurodegenerative diseases. The aim of the study was to examine the lymphocyte subpopulations, nonclassical Т cells, as well as cytokine production in patients with 3 stage PD complicated by motor fluctuations. Materials and methods. We examined 20 patients with 3 stage PD receiving dopaminergic combination therapy (main group) and 20 age-matched patients with chronic cerebrovascular disease (comparison group). Considering the suspected role of chronic constipation in maintaining dysbiosis and chronic inflammation in patients with PD, the presence of constipation was an inclusion criterion for this study. The subpopulation profile of the peripheral blood lymphocytes was assessed using flow cytofluorometry, as well as cytokine levels using enzyme linked immunosorbent assay. Results. It was found that the number of mature CD3+ T cells with or chains as the T-cell receptors (TCR) in the lymphocyte population was significantly lower in patients with PD median 74% (57.383.5)) than in the comparison group (median 80% (73.086.0); р = 0.014. There was also a statistically significant reduction in the number of CD3+CD56+ natural killer (NK) T cells in the group of patients with PD vs. the comparison group 4.7% (1.37.7) vs. 7.8% (0.824); р = 0.036. At the same time, the number of CD3CD56+ NK cells was significantly higher in the group of patients with PD (16.4% (934)) vs. the comparison group 8.7% (515); р = 0.001. Moreover, the main group had a statistically significantly higher number of activated CD3CD8+ NK cells 7% (4.513.5) vs. the comparison group 3.5% (0.864.9); р 0.001. Out of the total number of Т cells, the TCR CD4+CD8 subpopulation was statistically smaller in the group of patients with PD 13.6% (6.227.0) than in the comparison group 29.8% (4.052.1); р = 0.016. The study of cytokine levels in the group of patients with PD showed a significant increase in the induced production of interleukin-1 (IL-1), as well as a high (aberrant) spontaneous production of IL-10, which was 227.5 pg/ml in patients with PD when the normal range is 023 pg/ml. The correlation analysis showed that the TCR CD4+CD8 subpopulation and cytokines in the group of patients with PD had a statistically significant (p = 0.048) negative correlation with the induced production of IL-10 (r = 0.745) and a significant (p = 0.042) positive correlation with the induced production of the pro-inflammatory cytokine IL-1 (r = 0.648). There was a trend towards increased spontaneous production of IL-10 (r = 0.602; p = 0.0506) as the level of the TCR CD4+CD8 T helper cells decreased. Conclusion. Changes were found in the blood of patients with PD, which indicate a chronic inflammatory process: increased number of CD3CD56+ NK cells, including activated CD3CD8+ cells, and increased production of pro-inflammatory cytokine IL-1 and anti-inflammatory cytokine IL-10. A decrease was found in the level of a minor subpopulation of T cells, TCR CD4+CD8. The correlation found between this subpopulation and the production of pro- and anti-inflammatory cytokines indicates its role in regulation of chronic inflammation in PD.

Lymphotropic Viruses: Chronic Inflammation and Induction of Cancers.

Simple SummaryInfection with viruses such as HTLV-1, EBV and KSHV has been linked to many cancers, including leukemias and lymphomas in humans worldwide. These viruses establish life-long latency after initial infections. Currently, there are no effective treatments for the prevention of cancers associated with these viruses. Studies have shown that chronic inflammation mediated by the transcription factors STAT3 and NF-κB in HTLV-1, EBV and KSHV-infected cells play critical roles in the development of viral-associated cancers. Inhibition of STAT3 and NF-κB activation in cells harboring these latent viruses leads to their destruction and the production of new virus particles. De novo infection by these viruses induces rapid NF-κB and STAT3 activation and creates a favorable environment for virus entry into host cells and viral latency. However, the host factors and the mechanisms required for rapid NF-κB and STAT3 activation during de novo infection and latency by these viruses are largely unknown. In this review, we will discuss the mechanisms that are specifically involved in NF-κB and STAT3 activation during de novo infection and latency by KSHV, EBV and HTLV-1.Inflammation induced by transcription factors, including Signal Transducers and Activators of Transcription (STATs) and NF-κB, in response to microbial pathogenic infections and ligand dependent receptors stimulation are critical for controlling infections. However, uncontrolled inflammation induced by these transcription factors could lead to immune dysfunction, persistent infection, inflammatory related diseases and the development of cancers. Although the induction of innate immunity and inflammation in response to viral infection is important to control virus replication, its effects can be modulated by lymphotropic viruses including human T-cell leukemia virus type 1 (HTLV-1), Κaposi’s sarcoma herpesvirus (KSHV), and Epstein Barr virus (EBV) during de novo infection as well as latent infection. These lymphotropic viruses persistently activate JAK-STAT and NF-κB pathways. Long-term STAT and NF-κB activation by these viruses leads to the induction of chronic inflammation, which can support the persistence of these viruses and promote virus-mediated cancers. Here, we review how HTLV-1, KSHV and EBV hijack the function of host cell surface molecules (CSMs), which are involved in the regulation of chronic inflammation, innate and adaptive immune responses, cell death and the restoration of tissue homeostasis. Thus, better understanding of CSMs-mediated chronic activation of STATs and NF-κB pathways in lymphotropic virus-infected cells may pave the way for therapeutic intervention in malignancies caused by lymphotropic viruses.

The Crosstalk between Prostate Cancer and Microbiota Inflammation: Nutraceutical Products Are Useful to Balance This Interplay?

The human microbiota shows pivotal roles in urologic health and disease. Emerging studies indicate that gut and urinary microbiomes can impact several urological diseases, both benignant and malignant, acting particularly on prostate inflammation and prostate cancer. Indeed, the microbiota exerts its influence on prostate cancer initiation and/or progression mechanisms through the regulation of chronic inflammation, apoptotic processes, cytokines, and hormonal production in response to different pathogenic noxae. Additionally, therapies’ and drugs’ responses are influenced in their efficacy and tolerability by microbiota composition. Due to this complex potential interconnection between prostate cancer and microbiota, exploration and understanding of the involved relationships is pivotal to evaluate a potential therapeutic application in clinical practice. Several natural compounds, moreover, seem to have relevant effects, directly or mediated by microbiota, on urologic health, posing the human microbiota at the crossroad between prostatic inflammation and prostate cancer development. Here, we aim to analyze the most recent evidence regarding the possible crosstalk between prostate, microbiome, and inflammation.

The G Protein-Coupled Receptor (GPR) 15 Counteracts Antibody-Mediated Skin Inflammation

The G protein-coupled receptor 15 (GPR15) has recently been highlighted as an important regulator of T cell trafficking into the gut under physiological and pathophysiological conditions. Additionally, circumstantial evidence has accumulated that GPR15 may also play a role in the regulation of chronic inflammation. However, the (patho)physiological significance of GPR15 has, in general, remained rather enigmatic. In the present study, we have addressed the role of GPR15 in the effector phase of autoantibody-mediated skin inflammation, specifically in the antibody transfer mouse model of bullous pemphigoid-like epidermolysis bullosa acquisita (BP-like EBA). Subjecting Gpr15−/− mice to this model, we have uncovered that GPR15 counteracts skin inflammation. Thus, disease was markedly aggravated in Gpr15−/− mice, which was associated with an increased accumulation of γδ T cells in the dermis. Furthermore, GPR15L, the recently discovered cognate ligand of GPR15, was markedly upregulated in inflamed skin. Collectively, our results highlight GPR15 as counter-regulator of neutrophilic, antibody-mediated cutaneous inflammation. Enhancing the activity of GPR15 may therefore constitute a novel therapeutic principle in the treatment of pemphigoid diseases, such as BP-like EBA.

Association between dietary inflammatory index and serum C-reactive protein concentrations in the Japan Collaborative Cohort Study.

ABSTRACTDiet plays an important role in the regulation of chronic inflammation, which is linked to cardiovascular disease (CVD) and several cancers. The dietary inflammatory index (DII®) was developed to estimate the inflammatory potential of an individual’s diet. We examined the association between DII scores and serum high-sensitivity C-reactive protein (hs-CRP) concentrations using the baseline data from the Japan Collaborative Cohort Study (JACC Study). Data were from 1176 control subjects (650 men and 526 women) in a nested case-control study of several cancers and CVD in the JACC Study who were free of cancer and CVD at baseline. DII scores were calculated from 26 food parameters that were derived from a validated food frequency questionnaire administered at the baseline. Energy-adjusted DII scores were calculated using the residual method. Serum hs-CRP concentrations were measured by latex-enhanced nephelometry or enzyme-immunoassay. In multivariable logistic regression analysis adjusting for potential confounders including sex, age, smoking habits, drinking habits, body mass index, and history of hypertension, the odds ratio (OR) and 95% confidence intervals (CI) for high serum hs-CRP concentrations (>1.0 mg/L) was significantly higher in the highest versus the lowest DII quartile (ORQuartile4vs1 = 1.32, 95% CI = 1.01 to 2.52). Likewise, a 1-point increase in DII score was associated with a 14% increased risk of high serum hs-CRP concentrations (ORContinuous = 1.09, 95%CI = 1.01 to 1.19). A pro-inflammatory diet, as represented by high DII scores, was associated with high serum hs-CRP concentrations in this Japanese population.

Gene Expression Profiles for Macrophage in Tissues in Response to Different Exercise Training Protocols in Senescence Mice.

Age-induced chronic inflammation is prevented by aerobic and resistance exercise training. However, the effects of the mechanism of exercise on chronic inflammation in each tissue remains unclear. The aim of this study was to investigate the effects of resistance and aerobic training on gene expression profiles for macrophage infiltration and polarization (M1/M2 ratio) with chronic inflammation in various tissues of aged model mice. Male 38-week-old SAMP1 (senescence-accelerated prone mouse 1) mice were randomly divided into three groups—sedentary (Aged-Sed-SAMP1), aerobic training (Aged-AT-SAMP1; voluntary running), and resistance training—for 12 weeks (Aged-RT-SAMP1; climbing ladder). Resistance and aerobic exercise training prevented an increase in circulating TNF-α levels (a marker of systemic inflammation) in aged SAMP1 mice, along with decreases in tissue inflammatory cytokine (TNF-α and IL-1β) mRNA expression in the heart, liver, small intestine, brain, aorta, adipose, and skeletal muscle, but it did not change the levels in the lung, spleen, and large intestine. Moreover, resistance and aerobic exercise training attenuated increases in F4/80 mRNA expression (macrophage infiltration), the ratio of CD11c/CD163 mRNA expression (M1/M2 macrophage polarization), and MCP-1 mRNA expression (chemokine: a regulator of chronic inflammation) in the chronic inflamed tissues of aged SAMP1 mice. These results suggested that resistance and aerobic exercise training-induced changes in gene expression for macrophage infiltration and polarization in various tissues might be involved in the prevention of age-related tissue chronic inflammation, and lead to a reduction of the increase in circulating TNF-α levels, as a marker of systemic inflammation, in aged SAMP1 mice.

Chronic Stress, Inflammation, and Colon Cancer: A CRH System-Driven Molecular Crosstalk.

Chronic stress is thought to be involved in the occurrence and progression of multiple diseases, via mechanisms that still remain largely unknown. Interestingly, key regulators of the stress response, such as members of the corticotropin-releasing-hormone (CRH) family of neuropeptides and receptors, are now known to be implicated in the regulation of chronic inflammation, one of the predisposing factors for oncogenesis and disease progression. However, an interrelationship between stress, inflammation, and malignancy, at least at the molecular level, still remains unclear. Here, we attempt to summarize the current knowledge that supports the inseparable link between chronic stress, inflammation, and colorectal cancer (CRC), by modulation of a cascade of molecular signaling pathways, which are under the regulation of CRH-family members expressed in the brain and periphery. The understanding of the molecular basis of the link among these processes may provide a step forward towards personalized medicine in terms of CRC diagnosis, prognosis and therapeutic targeting.

The CD16A and CD16B mRNA level as potential immunological marker in colorectal cancer

The purpose of this study is to evaluate mRNA levels of genes encoding CD16A (FCGR3A) and CD16B (FCGR3B) in peripheral blood and tumors of colorectal cancer patients (CRC).Materials and methods. The study included 66 CRC patients from Nizhny Novgorod Regional Clinical Oncology Center and 111 people without cancer as a comparison group from Nizhny Novgorod Regional Blood Center named after N.Ya. Klimova. The mRNA relative levels in peripheral blood and tumor was detected by reverse transcription real-time polymerase chain reaction. The mRNA levels correlation and association with CRC clinical characteristics were assessed by statistic methods.Results. The study suggests that in the peripheral blood of CRC patients the levels of mRNA FCGR3A and FCGR3B were statistically significantly lower than in healthy individuals. The mRNA levels remained low at 7–10 days after surgery. The FCGR3A mRNA normalized level in the blood and tumors of CRC patients, as well as in the blood of healthy individuals, was several times higher than the FCGR3B mRNA level. At the II stage of tumor development in CRC patients, the FCGR3A and FCGR3B mRNA levels were statistically significantly decreased, but as the tumor progressed is normalized. Moderate degree of tumor differentiation was also characterized by a drop in mRNA levels of the tested genes. Reduced FCGR3A and FCGR3B mRNA levels in the blood of patients were observed in the absence of metastases. In tumor samples, FCGR3A mRNA was tested in 95.5% of cases, FCGR3B mRNA in 68.2% of cases. Progression of CRC was accompanied by an increase in FCGR3A mRNA level in tumors, the FCGR3B mRNA level did not change. Positive correlation of FCGR3A mRNA level with TNF and FOXP3 mRNA levels was found, which indicates the possible involvement of FCGR3A in the regulation of chronic inflammation in tumors of CRC patients.Conclusion. Changes in mRNA levels of genes encoding CD16A (FCGR3A) and CD16B (FCGR3A) molecules were detected in blood and tumor samples. The results indicate the potential for their use as monitoring immunological markers in CRC.

Inflammatory potential of the diet and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Chronic inflammation plays a critical role in the pathogenesis of the 2 major types of gastric cancer. Several foods, nutrients, and nonnutrient food components seem to be involved in the regulation of chronic inflammation. We assessed the association between the inflammatory potential of the diet and the risk of gastric carcinoma, overall and for the 2 major subsites: cardia cancers and noncardia cancers. A total of 476,160 subjects (30% men, 70% women) from the European Investigation into Cancer and Nutrition (EPIC) study were followed for 14 y, during which 913 incident cases of gastric carcinoma were identified, including 236 located in the cardia, 341 in the distal part of the stomach (noncardia), and 336 with overlapping or unknown tumor site. The dietary inflammatory potential was assessed by means of an inflammatory score of the diet (ISD), calculated with the use of 28 dietary components and their corresponding inflammatory scores. The association between the ISD and gastric cancer risk was estimated by HRs and 95% CIs calculated by multivariate Cox regression models adjusted for confounders. The inflammatory potential of the diet was associated with an increased risk of gastric cancer. The HR (95% CI) for each increase in 1 SD of the ISD were 1.25 (1.12, 1.39) for all gastric cancers, 1.30 (1.06, 1.59) for cardia cancers, and 1.07 (0.89, 1.28) for noncardia cancers. The corresponding values for the highest compared with the lowest quartiles of the ISD were 1.66 (1.26, 2.20), 1.94 (1.14, 3.30), and 1.07 (0.70, 1.70), respectively. Our results suggest that low-grade chronic inflammation induced by the diet may be associated with gastric cancer risk. This pattern seems to be more consistent for gastric carcinomas located in the cardia than for those located in the distal stomach. This study is listed on the ISRCTN registry as ISRCTN12136108.

Regulators of Chronic Inflammation, Cytokines, and Neural Stimulation

Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan. Reprints: Masaaki Murakami, DVM, PhD, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo 060-0815, Japan (e-mail: [email protected]). Supported by research grants from Kakenhi; Takeda Science Foundation; Institute for Fermentation, Osaka; Mitsubishi Foundation; Tokyo Medical Research Foundation; Uehara Memorial Foundation; Akiyama Life Science Foundation; Chugai Pharmaceutical Co Ltd; Takeda Pharmaceutical Co Ltd; Shionogi Co Ltd; and Sumitomo Dainippon Pharmaceutical Co Ltd. Ono Pharmaceutical Co Ltd, Gene Techno Science, Timelapse Vision/Sanofi, AMED-SICP, and JAXA-JSF to M. Murakami. M. Murakami has received consultation fees from Takeda Pharmaceutical Co Ltd and funding for research from Chugai Pharmaceutical Co Ltd, Takeda Pharmaceutical Co Ltd, Shionogi Co Ltd, Sumitomo Dainippon Pharmaceutical Co Ltd, Ono Pharmaceutical Co Ltd, Gene Techno Science, and Timelapse Vision/Sanofi.

Levels of osteopontin in plasma and tissue in relation to metabolic status in patients with lichen planus

Chronic inflammation with lichen planus (LP) has been suggested as a component of the metabolic syndrome (MetS). LP is assumed to be related closely to dyslipidemia. Plasma osteopontin (OPN) has been reported to be a potential clinical marker for the prediction of atherosclerosis. Selenium (Se), an essential trace element, involved in the defense against oxidative stress, has been hypothesized to prevent cardiovascular disease (CVD). Se compounds are effective in the downregulation of OPN expression. Moreover, an inverse relation has been detected between the levels of plasma OPN and plasma Se in patients with psoriasis. To determine the possible role of OPN and Se in the pathogenesis of LP and their relation to the metabolic status in patients. Thirty patients with LP and 30 controls were included. Participants were assessed for the presence of MetS and/or its components. In all participants, plasma and tissue OPN levels were assessed using an enzyme-linked immunosorbant assay, plasma Se levels were assessed by flame atomic absorption spectrophometry, and high-sensitivity C-reactive protein levels were assessed using a solid-phase enzyme-linked immunosorbant assay. Patients with LP showed a significant association with MetS parameters than the controls. Plasma and tissue OPN were significantly higher in LP patients than those in the control group. Plasma Se levels were significantly lower in patients than those in the control group. In patients, plasma OPN levels were associated positively with the presence of diabetes mellitus, dyslipidemia, and MetS. The presence of LP in patients was associated strongly with MetS parameters, most probably because of long-standing inflammation. OPN may be a critical regulator of chronic inflammation in patients with LP and may explain its association with components of the MetS such as diabetes mellitus and dyslipidemia.

Association of diet quality with dietary inflammatory potential in youth

ABSTRACTBackground: Diet plays a crucial role in the regulation of chronic inflammation. The sparse evidence available in adult populations indicates that diet quality is linked to the dietary inflammatory potential; however, this association has not been established in youth.Design: Data were obtained from a representative national sample of 2889 children and young people in Spain, aged 6–24 years. The dietary inflammatory potential was measured by the dietary inflammatory index (DII), and diet quality by three conceptually different measures: the Mediterranean Diet Quality Index for children and adolescents (KIDMED), energy density, and total dietary antioxidants capacity.Results: The mean DII was 1.96 ± 0.76 units Scoring for the KIDMED index and the total dietary antioxidant capacity significantly decreased (p < 0.001 and p = 0.030, respectively) across quintiles of the DII, whereas the opposite was true for energy density (p < 0.001). The effect size of these associations was strongest for energy density, followed by the KIDMED index and total dietary antioxidant capacity.Conclusion: A healthy diet characterized by high adherence to the Mediterranean diet, high total dietary antioxidant capacity, or low energy density was linked to greater anti-inflammatory potential of the diet, as measured by the DII.

Myeloid‑derived suppressor cells in bronchoalveolar lavage fluid in patients with chronic obstructive pulmonary disease.

INTRODUCTION Myeloid‑derived suppressor cells (MDSCs) have the potent ability to suppress T‑cell function, and are important in the regulation of chronic inflammation and carcinogenesis. MDSCs may influence local and systemic inflammation and carcinogenesis in COPD; however, their presence in bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) or their relationship with clinical parameters in COPD has not been studied yet. OBJECTIVES The aim of the study was to assess MDSCs in BALF and PB and to analyze the relationship between MDSCs and clinical parameters in COPD. PATIENTS AND METHODS The study included 64 patients with stable COPD. The clinical parameters of the patients were studied, and MDSCs were assessed using monoclonal antibodies directly conjugated with fluorochromes in flow cytometry. RESULTS The percentage of MDSCs in BALF was lower than that in PB (0.63 ±0.90 vs 3.94 ±0.38). In BALF, MDSCs (% of mononuclear cells) correlated with forced expiratory volume in 1 second (rs = -0.30, P = 0.0185), residual volume/total lung capacity (rs = 0.32, P = 0.0148), PaO2 (rs = -0.45, P = 0.0002), arterial oxygen saturation (SaO2; rs = -0.41, P = 0.0008), and diffusion capacity of carbon dioxide (rs = -0.32, P = 0.0211). There was a significant negative correlation between MDSCs (% of all leukocytes) and arterial oxygen pressure (rs = -0.42, P = 0.0006) and SaO2 (rs = -0.37, P = 0.0027). No correlations were found in PB. CONCLUSIONS MDSCs are present in human lung microenvironment and may be involved in local inflammation in COPD. Future studies should focus on a detailed assessment of MDSCs in local and systemic inflammation in COPD.

The expression of thymosin β4 in chronic hepatitis B combined nonalcoholic fatty liver disease.

The aim of the study was to detect the expression level of thymosin β4 (Tβ4) in serum and tissues of patients with chronic hepatitis B (CHB) combined nonalcoholic fatty liver disease (NAFLD). The effects of Tβ4 in hepatic steatosis, chronic inflammation, and fibrosis development in CHB combined NAFLD patients were also discussed. The study included 46 patients in the case group with CHB and NAFLD and 42 patients in the control group with CHB. ELISA was applied to detect serum Tβ4 and TNF-α level. Furthermore, the correlation analysis of Tβ4 levels with biochemical index, pathological index, and TNF-α level was performed. The Tβ4 immunohistochemical levels of different inflammation fibrosis levels were compared, and the correlation analysis with TNF expression was performed. The Tβ4 levels in patients with CHB combined NAFLD showed no statistical difference when compared to the control group. In patients with CHB combined NAFLD group, the Tβ4 level had no correlation with ALT, AST, TG, FGP, hepatitis B virus (HBV)-DNA levels, and fat grading, but had negative correlation with inflammation score and fibrosis score (P <0.01). The immunohistochemical results of hepatic tissues showed that the expression intensity of severe inflammation fibrosis group had statistical significance compared with that of slight group, and the Tβ4 expression both in serum and in liver tissue negatively correlated with TNF-α expression. Tβ4 could be involved in the regulation of chronic inflammation and fibrosis and plays a defense role in the disease progression of CHB combined NAFLD patients.

Chronic NF-κB activation links COPD and lung cancer through generation of an immunosuppressive microenvironment in the lungs.

Nuclear Factor (NF)-κB is positioned to provide the interface between COPD and carcinogenesis through regulation of chronic inflammation in the lungs. Using a tetracycline-inducible transgenic mouse model that conditionally expresses activated IκB kinase β (IKKβ) in airway epithelium (IKTA), we found that sustained NF-κB signaling results in chronic inflammation and emphysema by 4 months. By 11 months of transgene activation, IKTA mice develop lung adenomas. Investigation of lung inflammation in IKTA mice revealed a substantial increase in M2-polarized macrophages and CD4+/CD25+/FoxP3+ regulatory T lymphocytes (Tregs). Depletion of alveolar macrophages in IKTA mice reduced Tregs, increased lung CD8+ lymphocytes, and reduced tumor numbers following treatment with the carcinogen urethane. Alveolar macrophages from IKTA mice supported increased generation of inducible Foxp3+ Tregs ex vivo through expression of TGFβ and IL-10. Targeting of TGFβ and IL-10 reduced the ability of alveolar macrophages from IKTA mice to induce Foxp3 expression on T cells. These studies indicate that sustained activation of NF-κB pathway links COPD and lung cancer through generation and maintenance of a pro-tumorigenic inflammatory environment consisting of alternatively activated macrophages and regulatory T cells.

Experimental mouse models of T cell-dependent inflammatory bowel disease.

Inflammatory bowel diseases (IBD) represent idiopathic chronic inflammatory disorders of the intestinal tract that are associated with aberrant immune responses against intestinal bacteria. Here, we describe two T cell-dependent models of experimental murine IBD. In the "T cell transfer" model, lymphopenic (scid or Rag (-/-) ) mice develop colitis upon adoptive transfer of naïve CD4(+) T cells. This model has also been extensively employed to identify mechanisms through which CD4(+)CD25(+) regulatory T cells suppress intestinal inflammation in vivo. We also describe a model of T cell-dependent IBD in immunocompetent mice, induced by infection with the intestinal bacterium Helicobacter hepaticus and concomitant treatment with a blocking αIL-10R mAb, which leads to the development of chronic inflammation of the caecum and colon (typhlocolitis). Both models reproduce many facets of human IBD pathology, including epithelial hyperplasia, goblet cell depletion, and leukocyte infiltration. These models provide reliable and tractable systems for the analyses of the induction and regulation of chronic inflammation in the gut.