Feiyangchangweiyan capsule protects against ulcerative colitis in mice by modulating the OSM/OSMR pathway and improving gut microbiota.

BACKGROUND: Feiyangchangweiyan capsule (FYC) is a traditional Chinese medicine formulation used in the clinical treatment of acute and chronic gastroenteritis and bacterial dysentery. However, the effect of FYC on ulcerative colitis (UC) and the mechanism thereof remains unknown. PURPOSE: To investigate the protective effect of FYC on UC mice induced by dextran sulfate sodium and illustrate the potential mechanism of this effect. METHODS: Here, we established a model of UC mice by dextran sulfate sodium and administered with FYC. The disease activity index (DAI), colon length, myeloperoxidase (MPO) content in serum, pathological structure and ultrastructural changes, and inflammatory cell infiltration of colon tissue were evaluated. Transcriptome and 16S rDNA sequencing were employed to illuminate the mechanism of FYC in the protection of UC mice. RESULTS: FYC significantly alleviates the pathological damage and the infiltration of inflammatory cells in colon tissue of dextran sulfate sodium induced UC mice, rescues shortened colon length, reduces DAI score, MPO content in serum, and pro-inflammatory factors including IL-1ß, IL-6, CCL11, MCP-1 and MIP-2, and increases anti-inflammatory factors such as IL-10. Transcriptomics revealed that Oncostatin M (OSM) and its receptor (OSMR) are the critical pathway for UC treatment by FYC. OSM and OSMR increased in UC mice compared to control mice, and decreased with FYC, which was verified via measurement of OSM and OSMR mRNA and protein levels. Furthermore, we observed that FYC modulates intestinal microbiome composition (e.g., the proportion of Barnesiella/Proteobacteria) by affecting the inflammatory factors. CONCLUSION: FYC exerts an effect on UC by inhibiting the OSM/OSMR pathway and regulating inflammatory factors to improve the intestinal flora.

A grape seed extract maternal dietary supplementation in reproductive hens reduces oxidative stress associated to modulation of plasma and tissue adipokines expression and improves viability of offsprings.

In reproductive hens, a feed restriction is an usual practice to improve metabolic and reproductive disorders. However, it acts a stressor on the animal. In mammals, grape seed extracts (GSE) reduces oxidative stress. However, their effect on endocrine and tissue response need to be deepened in reproductive hens. Here, we evaluated the effects of time and level of GSE dietary supplementation on growth performance, viability, oxidative stress and metabolic parameters in plasma and metabolic tissues in reproductive hens and their offsprings. We designed an in vivo trial using 4 groups of feed restricted hens: A (control), B and C (supplemented with 0.5% and 1% of the total diet composition in GSE since week 4, respectively) and D (supplemented with 1% of GSE since the hatch). In hens from hatch to week 40, GSE supplementation did not affect food intake and fattening whatever the time and dose of supplementation. Body weight was significantly reduced in D group as compared to control. In all hen groups, GSE supplementation decreased plasma oxidative stress index associated to a decrease in the mRNA expression of the NOX4 and 5 oxidant genes in liver and muscle and an increase in SOD mRNA expression. This was also associated to decreased plasma chemerin and increased plasma adiponectin and visfatin levels. Interestingly, maternal GSE supplementation increased the live body weight and viability of chicks at hatching and 10 days of age. This was associated to a decrease in plasma and liver oxidative stress parameters. Taken together, GSE maternal dietary supplementation reduces plasma and tissue oxidative stress associated to modulation of adipokines without affecting fattening in reproductive hens. A 1% GSE maternal dietary supplementation increased offspring viability and reduced oxidative stress suggesting a beneficial transgenerational effect and a potential use to improve the quality of the progeny in reproductive hens.

Expression of Chemerin and Its Receptors in the Porcine Hypothalamus and Plasma Chemerin Levels during the Oestrous Cycle and Early Pregnancy.

Chemerin (CHEM) may act as an important link integrating energy homeostasis and reproductive functions of females, and its actions are mediated by three receptors: chemokine-like receptor 1 (CMKLR1), G protein-coupled receptor 1 (GPR1), and C-C motif chemokine receptor-like 2 (CCRL2). The aim of the current study was to compare the expression of CHEM and its receptor (CHEM system) mRNAs (quantitative real-time PCR) and proteins (Western blotting and fluorescent immunohistochemistry) in the selected areas of the porcine hypothalamus responsible for gonadotropin-releasing hormone production and secretion: the mediobasal hypothalamus, preoptic area and stalk median eminence during the oestrous cycle and early pregnancy. Moreover, plasma CHEM concentrations were determined using ELISA. The expression of CHEM system has been demonstrated in the porcine hypothalamus throughout the luteal phase and follicular phase of the oestrous cycle, and during early pregnancy from days 10 to 28. Plasma CHEM levels and concentrations of transcripts and proteins of CHEM system components in the hypothalamus fluctuated throughout pregnancy and the oestrous cycle. Our study was the first experiment to demonstrate the presence of CHEM system mRNAs and proteins in the porcine hypothalamus and the correlations between the expression levels and physiological hormonal milieu related to the oestrous cycle and early pregnancy.

Utility of chemokines CCL2, CXCL8, 10 and 13 and interleukin 6 in the pediatric cohort for the recognition of neuroinflammation and in the context of traditional cerebrospinal fluid neuroinflammatory biomarkers.

BACKGROUND: The recognition of active inflammation in the central nervous system (CNS) in the absence of infectious agents is challenging. The present study aimed to determine the diagnostic relevance of five selected chemo/cytokines in the recognition of CNS inflammation and in the context of traditional cerebrospinal fluid (CSF) biomarkers (white blood cell [WBC] counts, oligoclonal bands, protein levels, CSF/serum albumin ratios) and clinical diagnoses. METHODS: C-C and C-X-C motif ligands (CCL2, CXCL8, 10 and 13) and interleukin (IL) 6 levels in the CSF and serum from 37 control and 87 symptomatic children with ten different (mostly noninfectious) inflammatory CNS disorders (16 of which had follow-up samples after recovery) were determined using Luminex multiple bead technology and software. Nonparametric tests were used; p < 0.05 was considered statistically significant. Receiver operating characteristic curves were constructed to analyze controls and 1) all symptomatic samples or 2) symptomatic samples without CSF pleocytosis. RESULTS: Compared with the control CSF samples, levels of all investigated chemo/cytokines were increased in symptomatic CSF samples, and only IL-6 remained elevated in recovery samples (p ≤ 0.001). CSF CXCL-13 levels (> 10.9 pg/mL) were the best individual discriminatory criterion to differentiate neuroinflammation (specificity/sensitivity: 97/72% and 97/61% for samples without pleocytosis), followed by CSF WBC counts (specificity/sensitivity: 97/62%). The clinical utility of the remaining CSF chemo/cytokine levels was determined in descending order of sensitivities corresponding to thresholds that ensured 97% specificity for neuroinflammation in samples without pleocytosis (pg/mL; sensitivity %): IL-6 (3.8; 34), CXCL8 (32; 26), CXCL10 (317; 24) and CCL2 (387; 10). Different diagnosis-related patterns of CSF chemo/cytokines were observed. CONCLUSIONS: The increased CSF level of CXCL13 was the marker with the greatest predictive utility for the general recognition of neuroinflammation among all of the individually investigated biomarkers. The potential clinical utility of chemo/cytokines in the differential diagnosis of neuroinflammatory diseases was identified.

Effects of Desloratadine Citrate Disodium on Serum Immune Function Indices, Inflammatory Factors and Chemokines in Patients with Chronic Urticaria.

OBJECTIVE: To determine the effects of desloratadine citrate disodium on serum immunological function indices (IgE, C3 and C4), inflammatory factors (IL-4, IL-17 and IL-33), and chemokines (MCP-1, RANTES and Eotaxin) in patients with chronic urticaria. STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Department of Dermatology, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi'an, China, from January 2017 to January 2018. METHODOLOGY: A total of 128 patients with chronic urticaria were randomly divided into a control group and an observation group, with 64 patients in each group. The patients in the control group were treated with loratadine and those in the observation group were treated with desloratadine citrate disodium. After 4 weeks of treatment, the serum levels of immune function indices (IgE, C3 and C4), inflammatory factors (IL-4, IL-17 and IL-33), and chemokines (MCP-1, RANTES and Eotaxin) were determined. RESULTS: After 4 weeks of treatment, the levels of serum IgE, IL-4, IL-17, IL-33, MCP-1, RANTES and Eotaxin in the observation group were lower than those in the control group (all p<0.001). The levels of serum C3 and C4 in the observation group were higher than those in the control group (both p<0.001). CONCLUSION: Desloratadine citrate disodium can effectively reduce the severity of chronic urticaria, and its therapeutic mechanism may be related to balancing Th1/Th2 cell function, regulating inflammatory mediators and inhibiting the action of chemokines.

Protective effect of vitamin D supplementation in a rat modal of preeclampsia: a possible implication of chemerin.

Background: Preeclampsia (PE) is a disorder of pregnancy associated with vitamin D (VD) deficiency. Chemerin is an adipokine significantly increased in preeclampsia and is regulated by VD. Objectives: To determine whether VD supplementation would protect against development of PE through Chemerin reduction Methods: PE was induced in albino rats by injection of 12.5 mg of deoxycorticosterone (DOCA).   Rats were randomly divided into normal pregnant, PE group, VD supplemented PE group. Results: VD supplementation decreased systolic blood pressure, proteinuria and decreased serum Chemerin level. Conclusion: VD treatment reduced Chemerin level, and blood pressure in DOCA rat model of PE.

Arsenic-induced inflammation in workers.

Occupational and environmental exposures to metal and metalloids can result in neurotoxicity and immunotoxicity. Selenium (Se) is essential for the proper functioning of neutrophils, macrophages, natural killer (NK) cells, T-lymphocytes and other immune mechanisms, while zinc (Zn) is a trace element essential for basic cell activities, including cell growth and differentiation. Arsenic (As) may lead to different types of immunosuppressive effects. This study consisted of 62 male workers, who had been exposed to arsenic for different durations and 73 non-exposed male workers (control group) with no history of occupational toxic metal exposure. Whole blood and serum samples were taken from each participant for immunological, toxicological and routine analysis during their annual periodical examination. Arsenic, selenium and zinc levels were determined by the ICP-MS and cytokines, IL-6, IL-10, TNF-α, sE-selectin and VCAM-1, were measured by ELISA. There were statistically significant differences (p < 0.001) between control and As-exposed group in As (1.37 ± 0.42 vs. 4.27 ± 1.54 µg/L) and Se levels (106.37 ± 48.04 vs. 74.70 ± 30.45 µg/L). The changing levels of As, Zn and Se seems to affect the severity of inflammatory reactions based on IL-6, IL-10 and TNF-α levels (r = 0.755, r = 0.679 and r = 0.617, respectively, for all p < 0.01). Selenium was found to have a suppressive effect on cytokines, as evidenced by Pearson correlations and regression analysis. These findings support the need to closely monitor Se levels in individuals exposed to arsenic and benefits for Se supplementation in the case of arsenic exposure, occupationally or environmentally.

Elevated serum chemokines are independently associated with both endometriosis and uranium exposure.

Endometriosis is a complex disease impacted by the hormonal and immune systems. Cytokines and chemokines are serum biomarkers that maybe useful to develop a noninvasive disease diagnosis. Individuals in the Fernald Community Cohort were exposed to uranium, a heavy metal with radioactive properties and estrogenic potential; therefore, serum samples from women in this cohort with or without uranium and with or without endometriosis were compared for alterations in chemokine, cytokine, and matrix metalloproteinase (MMP) levels. Control women were matched to endometriosis cases by uranium exposure, age, and body mass index. MMP levels were not altered. Five chemokines and one cytokine significantly increased in endometriosis cases versus controls irrespective of uranium exposure. Uranium exposure alone was associated with an increase in inflammatory chemokines. The majority of the elevated chemokines in endometriosis cases play important roles in attracting T helper-2 cells, which may be vital to understanding the immune response in endometriosis.

Dietary Cellulose Supplementation Modulates the Immune Response in a Murine Endotoxemia Model.

The role of dietary fiber in chronic inflammatory disorders has been explored, but very little is known about its benefits in acute inflammation. Previously, we have demonstrated that dietary cellulose supplementation confers protection in a murine model of sepsis by promoting the growth of the gut microbiota that are linked to metabolic health. The survival benefit is associated with a decrease in serum concentration of proinflammatory cytokines, reduced neutrophil infiltration in the lungs, and diminished hepatic inflammation. Here, we aim to understand if the benefit of manipulating the gut microbiome exerts a broader "systemic" influence on the immune system in a lethal murine endotoxemia model. We hypothesize that mice-fed high-fiber cellulose (HF) diet will demonstrate a reduction in activated macrophages and dendritic cells (DCs) and a concomitant increase in the suppressive capacity of T-regulatory cells (Tregs) toward T cells responsiveness. We characterized the immunological profile and activation status of macrophages, DCs, and T cells in mice on HF diet that were then subjected to endotoxemia. Supplementation with HF diet decreased the number and activation of splenic macrophages and DCs in mice after LPS administration. Similarly, HF diet amplified the suppressive function of Tregs and induced anergy in T cells as compared with mice on a regular diet. Our data suggest that the use of HF diet can be a simple, yet effective tool that decreases the hepatic DNA-binding activity of NF-κB leading to a reduction in proinflammatory cytokine response in a murine endotoxemia model.

The Role of Omega-3 Fatty Acids in the Setting of Coronary Artery Disease and COPD: A Review.

Chronic obstructive pulmonary disease (COPD) is a growing healthcare concern and will represent the third leading cause of death worldwide within the next decade. COPD is the result of a complex interaction between environmental factors, especially cigarette smoking, air pollution, and genetic preconditions, which result in persistent inflammation of the airways. There is growing evidence that the chronic inflammatory state, measurable by increased levels of circulating cytokines, chemokines, and acute phase proteins, may not be confined to the lungs. Cardiovascular disease (CVD) and especially coronary artery disease (CAD) are common comorbidities of COPD, and low-grade systemic inflammation plays a decisive role in its pathogenesis. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) exert multiple functions in humans and are crucially involved in limiting and resolving inflammatory processes. n-3 PUFAs have been intensively studied for their ability to improve morbidity and mortality in patients with CVD and CAD. This review aims to summarize the current knowledge on the effects of n-3 PUFA on inflammation and its impact on CAD in COPD from a clinical perspective.

Phosphodiesterase 4 inhibition reduces lung fibrosis following targeted type II alveolar epithelial cell injury.

Fibrosis of the lung constitutes a major clinical challenge and novel therapies are required to alleviate the associated morbidity and mortality. Investigating the antifibrotic efficacy of drugs that are already in clinical practice offers an efficient strategy to identify new therapies. The phosphodiesterase 4 (PDE4) inhibitors, approved for the treatment of chronic obstructive pulmonary disease, harbor therapeutic potential for pulmonary fibrosis by augmenting the activity of endogenous antifibrotic mediators that signal through cyclic AMP. In this study, we tested the efficacy of several PDE4 inhibitors including a novel compound (Compound 1) in a murine model of lung fibrosis that results from a targeted type II alveolar epithelial cell injury. We also compared the antifibrotic activity of PDE4 inhibition to the two therapies that are FDA-approved for idiopathic pulmonary fibrosis (pirfenidone and nintedanib). We found that both preventative (day 0-21) and therapeutic (day 11-21) dosing regimens of the PDE4 inhibitors significantly ameliorated the weight loss and lung collagen accumulation that are the sequelae of targeted epithelial cell damage. In a therapeutic protocol, the reduction in lung fibrosis with PDE4 inhibitor administration was equivalent to pirfenidone and nintedanib. Treatment with this class of drugs also resulted in a decrease in plasma surfactant protein D concentration, a reduction in the plasma levels of several chemokines implicated in lung fibrosis, and an in vitro inhibition of fibroblast profibrotic gene expression. These results motivate further investigation of PDE4 inhibition as a treatment for patients with fibrotic lung disease.

An Extract of Artemisia dracunculus L. Promotes Psychological Resilience in a Mouse Model of Depression.

Stress-induced peripheral inflammation contributes to depression-like behaviors in both human and experimental models. PMI 5011, a botanical extract of Artemisia dracunculus L., was previously shown to have multiple bioactivities, including anti-inflammatory activity. In this work, using a repeated social defeat stress (RSDS) model of depression, we demonstrate that oral administration of the botanical extract PMI 5011 promotes resilience to RSDS-mediated depression-like phenotypes. We also show that the behavioral improvements are associated with attenuation of stress-mediated induction of inflammatory cytokines in the periphery and alteration of synaptic plasticity in the nucleus accumbens (NAc). Our studies provide experimental evidence that botanical extracts such as PMI 5011, which target pathological mechanisms (i.e., peripheral inflammation) not addressed by currently available antidepressants, could be further developed as novel therapeutics for the treatment of stress disorders and anxiety in humans.

Yirui Capsules Alleviate Atherosclerosis by Improving the Lipid Profile and Reducing Inflammation in Apolipoprotein E-Deficient Mice.

Atherosclerosis (AS) is the main cause of cardiovascular diseases. This study investigated Yirui (YR) capsules, whose ingredients are available in health food stores, against AS and the underlying mechanisms. Male apolipoprotein E-deficient mice fed a high-fat diet for 10 weeks developed severe aortic lesions, but YR significantly decreased the plaque area in the total aorta and aortic root. YR affected the serum lipid profile by significantly reducing total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and oxidative modification of LDL-C (Ox-LDL) levels. In addition, multi-cytokine analysis revealed that higher serum levels of interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1ß), interleukin-3 (IL-3), interleukin-6 (IL-6), interleukin-27 (IL-27), tumor necrosis factor alpha, interferon gamma, and regulated on activation, normal T cell expressed and secreted (RANTES), which were induced by a high-fat diet, declined with YR treatment. These results suggest that YR reduces the atherosclerotic plaque burden, thereby alleviating AS by modulating the lipid profile and inhibiting inflammation.

Yoga training modulates adipokines in adults with high-normal blood pressure and metabolic syndrome.

Metabolic syndrome (MetS) is associated with diabetes mellitus and cardiovascular diseases. Our previous study indicated that people with MetS showed a decrease in waist circumference and a decreasing trend in blood pressure after 1-year yoga. This study investigated the effect of yoga on MetS people with high-normal blood pressure by exploring modulations in proinflammatory adipokines (leptin, chemerin, visfatin, and plasminogen activator inhibitor-1 or PAI-1) and an anti-inflammatory adipokine (adiponectin). A total of 97 Hong Kong Chinese individuals aged 57.6 ± 9.1 years with MetS and high-normal blood pressure were randomly assigned to control (n = 45) and yoga groups (n = 52). Participants in the control group were not given any intervention but were contacted monthly to monitor their health status. Participants in the yoga group underwent a yoga training program with three 1-hour yoga sessions weekly for 1 year. The participants' sera were harvested and assessed for adipokines. Generalized estimating equation (GEE) was used to examine the interaction effect between 1-year time (pre vs post), and intervention (control vs yoga). GEE analyses revealed significant interaction effects between 1-year time and yoga intervention for the decreases in leptin and chemerin and the increase in adiponectin concentration in the sera examined. These results demonstrated that 1-year yoga training decreased proinflammatory adipokines and increased anti-inflammatory adipokine in adults with MetS and high-normal blood pressure. These findings support the beneficial role of yoga in managing MetS by favorably modulating adipokines.

Role of glucocorticoid-induced leucine zipper (GILZ) in inflammatory bone loss.

TNF-α plays a key role in the development of rheumatoid arthritis (RA) and inflammatory bone loss. Unfortunately, treatment of RA with anti-inflammatory glucocorticoids (GCs) also causes bone loss resulting in osteoporosis. Our previous studies showed that overexpression of glucocorticoid-induced leucine zipper (GILZ), a mediator of GC's anti-inflammatory effect, can enhance osteogenic differentiation in vitro and bone acquisition in vivo. To investigate whether GILZ could antagonize TNF-α-induced arthritic inflammation and protect bone in mice, we generated a TNF-α-GILZ double transgenic mouse line (TNF-GILZ Tg) by crossbreeding a TNF-α Tg mouse, which ubiquitously expresses human TNF-α, with a GILZ Tg mouse, which expresses mouse GILZ under the control of a 3.6kb rat type I collagen promoter fragment. Results showed that overexpression of GILZ in bone marrow mesenchymal stem/progenitor cells protected mice from TNF-α-induced inflammatory bone loss and improved bone integrity (TNF-GILZ double Tg vs. TNF-αTg, n = 12-15). However, mesenchymal cell lineage restricted GILZ expression had limited effects on TNF-α-induced arthritic inflammation as indicated by clinical scores and serum levels of inflammatory cytokines and chemokines.

[Current advance in cerebral malaria].

Cerebral malaria (CM), a severe neurological syndrome caused by Plasmodium falciparum infection, is a serious life-threatening disease with a high mortality. Survivors' persistent brain injury is manifested as long-term neurocognitive disorders. The main neuropathological feature of CM is the sequestration of parasited red blood cells (pRBCs) in cerebral microvessels. Other neuropathological features of CM include petechial hemorrhage in the brain parenchyma, annular hemorrhage, extensive brain endothelial cell activation, and focal endothelial cell injury and necrosis. However, its pathogenesis is still not clear. Currently, some studies have suggested that the pathogenesis of cerebral malaria mainly include pRBC adhesion, inflammatory reaction cascade, vascular leakage damage and brain hypoxia. Studies have shown that the biomarkers currently used as diagnostic and prognostic markers for CM include C-X-C motif chemokine ligand 10 (CXCL10), CXC chemokine ligand 4 (CXCL4), angiopoietin (Ang). In this paper, we systematically summarize the basic and clinical research for cerebral malaria in recent years and the latest literatures for drug studies, and focused on the advance of studies on cerebral malaria and its immunologic mechanism in the recent three years in the aspects of cytokines, immune cells, regulatory factors and biomarkers, so as to provide references for relevant studies.

Esculetin prevents non-alcoholic fatty liver in diabetic mice fed high-fat diet.

This study investigated the effects and mechanism of esculetin (6,7-dihydroxycoumarin) on non-alcoholic fatty liver in diabetic mice fed high-fat diet (HFD). The diabetic mice model was induced by injection of streptozotocin, after which they were fed HFD diet with or without esculetin for 11 weeks. Non-diabetic mice were provided a normal diet. Diabetes induced hepatic hypertrophy, lipid accumulation and droplets; however, esculetin reversed these changes. Esculetin treatment in diabetic mice fed HFD significantly down-regulated expression of lipid synthesis genes (Fasn, Dgat2 and Plpp2) and inflammation genes (Tlr4, Myd88, Nfkb, Tnfα and Il6). Moreover, the activities of hepatic lipid synthesis enzymes (fatty acid synthase and phosphatidate phosphohydrolase) and gluconeogenesis enzyme (glucose-6-phosphatase) in the esculetin group were decreased compared with the diabetic group. In addition, esculetin significantly reduced blood HbA1c, serum cytokines (TNF-α and IL-6) and chemokine (MCP-1) levels compared with the diabetic group without changing the insulin content in serum and the pancreas. Hepatic SOD activity was lower and lipid peroxidation level was higher in the diabetic group than in the normal group; however, esculetin attenuates these differences. Overall, these results demonstrated that esculetin supplementation could protect against development of non-alcoholic fatty liver in diabetes via regulation of lipids, glucose and inflammation.

Clinical Progression and Cytokine Profiles of Middle East Respiratory Syndrome Coronavirus Infection.

Clinical progression over time and cytokine profiles have not been well defined in patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. We included 17 patients with laboratory-confirmed MERS-CoV during the 2015 outbreak in Korea. Clinical and laboratory parameters were collected prospectively. Serum cytokine and chemokine levels in serial serum samples were measured using enzyme-linked immunosorbent assay. All patients presented with fever. The median time to defervescence was 18 days. Nine patients required oxygen supplementation and classified into severe group. In the severe group, chest infiltrates suddenly began to worsen around day 7 of illness, and dyspnea developed at the end of the first week and became apparent in the second week. Median time from symptom onset to oxygen supplementation was 8 days. The severe group had higher neutrophil counts during week 1 than the mild group (4,500 vs. 2,200/µL, P = 0.026). In the second week of illness, the severe group had higher serum levels of IL-6 (54 vs. 4 pg/mL, P = 0.006) and CXCL-10 (2,642 vs. 382 pg/mL, P < 0.001). IFN-α response was not observed in mild cases. Our data shows that clinical condition may suddenly deteriorate around 7 days of illness and the serum levels of IL-6 and CXCL-10 was significantly elevated in MERS-CoV patients who developed severe diseases.

Effects of Hovenia dulcis Thunb. extract and methyl vanillate on atopic dermatitis-like skin lesions and TNF-α/IFN-γ-induced chemokines production in HaCaT cells.

OBJECTIVES: Here, we hypothesized that Hovenia dulcis branch extract (HDB) and its active constituents ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis (AD)-like skin lesions by modulating the T helper Th1/Th2 balance in NC/Nga mice and TNF-α- and IFN-γ-induced production of thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) in HaCaT cells. METHODS: HaCaT cells were stimulated by TNF-α/IFN-γ in the presence of HDB and its constituents. TARC and MDC were measured by ELISA and RT-PCR. For the in-vivo study, oral feeding of HDB was performed for 5 weeks with 2,4-dinitrochlorobenzene (DNCB) treatment every other day. The efficacy of HDB on parameters of DNCB-induced AD was evaluated morphologically, physiologically and immunologically. KEY FINDINGS: In-vitro studies showed that HDB and its constituents suppressed TNF-α/IFN-γ-induced production of TARC and MDC in HaCaT cells by inhibiting MAPK signalling. In-vivo studies showed that HDB regulated immunoglobulin (Ig) E and immunoglobulin G2a (IgG2a) levels in serum and the expression of mRNA for Th1- and Th2-related mediators in skin lesions. Histopathological analyses revealed reduced epidermal thickness and reduced infiltration of skin lesions by inflammatory cells. CONCLUSION: These results suggest that HDB inhibits AD-like skin diseases by regulating Th1 and Th2 responses in NC/Nga mice and in HaCaT cells.

Coffee consumption modulates inflammatory processes in an individual fashion.

SCOPE: Anti-inflammatory effects of coffee consumption have been reported to be caused by caffeine and adenosine receptor signaling. However, contradictory effects have been observed. Many kinds of chronic diseases are linked to inflammation; therefore a profound understanding of potential effects of coffee consumption is desirable. METHODS AND RESULTS: We performed ex vivo experiments with eight individuals investigating peripheral blood mononuclear cells isolated from venous blood before and after coffee consumption, as well as in vitro experiments applying caffeine on isolated cells. After in vitro inflammatory stimulation of the cells, released cytokines, chemokines, and eicosanoids were determined and quantified using targeted mass spectrometric methods. Remarkably, the release of inflammation mediators IL6, IL8, GROA, CXCL2, CXCL5 as well as PGA2, PGD2, prostaglandin E2 (PGE2), LTC4, LTE4, and 15S-HETE was significantly affected after coffee consumption. While in several individuals coffee consumption or caffeine treatment caused significant downregulation of most inflammation mediators, in other healthy individuals exactly the opposite effects were observed. CONCLUSION: Ruling out age, sex, coffee consumption habits, the metabolic kinetics of caffeine in blood and the individual amount of regulatory T cells or CD39 expression as predictive parameters, we demonstrated here that coffee consumption may have significant pro- or anti-inflammatory effects in an individual fashion.