Production Of Chemical Mediators Research Articles

Development of a Radioiodinated Probe for in Vivo Detection of Lipid Radicals and Evaluation Using Middle Cerebral Artery Occlusion Model

Free radicals, such as hydroxyl radical, superoxide, and lipid-derived radical, have unpaired electrons, making them a highly reactive chemical species. They play important physiological roles, for example, in the removal of xenobiotic substances, such as bacteria and viruses, and in the production of chemical mediators, like prostaglandins and leukotrienes. However, excessive production of free radicals can cause structural defects in biomolecules like DNA and proteins, resulting in a loss of their normal functions. Hence, free radicals have been implicated in the onset and progression of various diseases such as cancer, atherosclerosis, and neurodegenerative diseases. However, there is very little clarity on the substantial amount, type, and location of free radicals in vivo, under pathological conditions. An investigation on the actual state of free radicals in vivo could lead to the diagnosis of pathological conditions and the elucidation of the mechanisms of their onset and progression; therefore, the development of in vivo radical detection methods is being widely pursued. Toward this end, nuclear medical imaging methods have recently attracted attention. In this study, we discuss the development of a nuclear medical imaging probe for the specific targeting of lipid radicals.

Omega-3 Polyunsaturated Fatty Acids and the Intestinal Epithelium-A Review.

Epithelial cells (enterocytes) form part of the intestinal barrier, the largest human interface between the internal and external environments, and responsible for maintaining regulated intestinal absorption and immunological control. Under inflammatory conditions, the intestinal barrier and its component enterocytes become inflamed, leading to changes in barrier histology, permeability, and chemical mediator production. Omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) can influence the inflammatory state of a range of cell types, including endothelial cells, monocytes, and macrophages. This review aims to assess the current literature detailing the effects of ω-3 PUFAs on epithelial cells. Marine-derived ω-3 PUFAs, eicosapentaenoic acid and docosahexaenoic acid, as well as plant-derived alpha-linolenic acid, are incorporated into intestinal epithelial cell membranes, prevent changes to epithelial permeability, inhibit the production of pro-inflammatory cytokines and eicosanoids and induce the production of anti-inflammatory eicosanoids and docosanoids. Altered inflammatory markers have been attributed to changes in activity and/or expression of proteins involved in inflammatory signalling including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator activated receptor (PPAR) α and γ, G-protein coupled receptor (GPR) 120 and cyclooxygenase (COX)-2. Effective doses for each ω-3 PUFA are difficult to determine due to inconsistencies in dose and time of exposure between different in vitro models and between in vivo and in vitro models. Further research is needed to determine the anti-inflammatory potential of less-studied ω-3 PUFAs, including docosapentaenoic acid and stearidonic acid.

Chamaecyparis obtusa Essential Oil Inhibits House Dust Mite Induced Nasal Epithelial Cell Activation and Immune Responses.

Essential oils extracted from plants contain protective volatile compounds and are known to processes antibacterial, antifungal, anti-oxidative, and anti-inflammatory effects. This study was conducted to explore the immunomodulatory effects of essential oil extracted from Chamaecyparis obtusa (EOCO) on house dust mite-induced mucosal inflammation. Cultured primary nasal epithelial cells were stimulated with Dermatophagoides pteronyssinus (DP), and Dermatophagoides farina (DF) for 48 h. The production of interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP) was measured by enzyme-linked immunosorbent assay, and the expression levels of nuclear factor (NF)-κB, activator protein (AP)-1, and mitogen-activated protein kinase (MAPK) were determined by western blot analysis. To examine the effect of EOCO on the production of chemical mediators and the expression of transcription factors, epithelial cells were pretreated with EOCO for 1 h before stimulation. Peripheral blood mononuclear cells (PBMCs) were cultured in nasal epithelial cell conditioned media (NECM) for 72 h, after which the levels of IL-5, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were measured. DP and DF enhanced the production of IL-25, IL-33, and TSLP, and EOCO pretreatment inhibited their production from nasal epithelial cells. EOCO pretreatment also significantly suppressed the expression of NF-κB and AP-1. NECM induced the production of IL-5, IFN- γ, and TNF-α from PBMCs, and only TNF-α production was significantly inhibited by EOCO pretreatment. EOCO pretreatment inhibited the DP and DF induced nasal epithelial cell derived cytokine production and TNF-α production from PBMCs. These results indicate the potential value of EOCO in the treatment of airway inflammatory or immunological diseases.

Comparison of Manuka, Kanuka, and Black Locust Honey on the Production of Chemical Mediators by Peripheral Blood Mononuclear Cells

Comparison of Manuka, Kanuka, and Black Locust Honey on the Production of Chemical Mediators by Peripheral Blood Mononuclear Cells

Ceramide-CD300f binding suppresses experimental colitis by inhibiting ATP-mediated mast cell activation

ObjectiveExtracellular ATP mediates mast cell-dependent intestinal inflammation via P2X7 purinoceptors. We have previously shown that CD300f (also called the leucocyte mono-immunoglobulin-like receptor 3 (LMIR3)) suppresses immunoglobulin E-dependent and mast cell-dependent...

The Effect of Omnaris® on the Inflammatory Reaction and Mucin Gene Expression from Nasal Polyp Epithelial Cells

Received December 13, 2013 Revised May 12, 2014 Accepted June 9, 2014 Address for correspondence Seung-Heon Shin, MD Department of OtolaryngologyHead and Neck Surgery, School of Medicine, Catholic University of Daegu, 33 Duryugongwon-ro 17-gil, Nam-gu, Daegu 705-718, Korea Tel +82-53-650-4530 Fax +82-53-650-4533 E-mail hsseung@cu.ac.kr Background and ObjectivesZZGlucocorticoids are a potent anti-inflammatory agent. The authors conducted this study to investigate the effect of Omnaris on suppression of inflammation induction and mucin gene expression in nasal polyp epithelial cells. Subjects and MethodZZPrimary nasal polyp epithelial cells were stimulated by 5 ug/mL of streptococcal enterotoxin B (SEB) and lipopolysaccharide (LPS). To determine the effects of Omnaris, cells were pretreated with 200, 100, 10, 1 ng/mL of Omnaris. The anti-inflammatory effect of epithelial cells were confirmed by measuring interleukin (IL)-6, IL-8, and granulocyte-macrophage colony stimulating factor (GM-CSF), and mucin gene expressions were determined by real time PCR for MUC4, MUC5AC, MUC5B, MUC8. ResultsZZSEB and LPS enhanced the production of IL-6, IL-8, and GM-CSF from nasal polyp epithelial cells. The increased cytokine levels were significantly suppressed by Omnaris at 100 and 10 ng/mL. The expressions of MUC4, MUC5AC, MUC5B, MUC8 mRNA, and MUC4 mRNA were increased by SEB and LPS, respectively. The increased expression of these mucin genes were significantly suppressed by 100, 10, and 1 ng/mL of Omnaris. ConclusionZZOmnaris significantly suppressed the production of chemical mediators and mucin gene expression, which indicated that Omnaris is effective in improving and treating inflammatory diseases in the nasal cavity. Korean J Otorhinolaryngol-Head Neck Surg 2014;57(9):603-9

Rhinovirus-infected nasal polyp epithelial cells: effect on the activation and migration of eosinophils by airborne fungi

Rhinovirus and fungi are common environmental factors able to induce airway inflammation. They are associated with the production of chemical mediators by direct activation of epithelial cells. To evaluate the effect of fungal stimulation of rhinovirus-infected nasal polyp epithelial cells (NPECs) on the activation and migration of eosinophils. Rhinovirus-infected NPECs were stimulated with Alternaria and Aspergillus for 48 hours. Then, epithelial cells were co-cultured with freshly isolated eosinophils. An eosinophil migration study was performed with epithelial cell-conditioned media. Interleukin 6, interleukin 8, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor levels were measured to determine the activation of cells. Airborne fungi enhanced the production of cytokines from rhinovirus 16-infected NPECs compared with fungi stimulation or rhinovirus 16 infection alone. Rhinovirus 16-infected NPECs were co-cultured with eosinophils, and cytokine production was not significantly increased except tumor necrosis factor-alpha production by Aspergillus. Epithelial cell-conditioned media, which were stimulated with fungi, enhanced the migration of eosinophils. There was some synergism between rhinovirus 16 infection and airborne fungal exposure, enhancing the inflammatory response of airway epithelial cells.

Effects of Bidens pilosa L. var. radiata SCHERFF treated with enzyme on histamine-induced contraction of guinea pig ileum and on histamine release from mast cells

The medical mechanism against type I allergies is to block the release or production of chemical mediators from mast cells or to block the H(1)-receptor signaling. We previously reported that the anti-allergic action of the dry powder from Bidens pilosa L. var. radiata SCHERFF treated with the enzyme cellulosine (eMMBP) was dependent on the inhibition of histamine release from mast cells. Here, we investigate that the effect of fractions in eMMBP on the histamine-induced contraction in guinea pig ileum and on the release of histamine in rat peritoneal mast cells. The histamine-induced contraction in guinea pig ileum is dose-dependently inhibited by ketotifen, an antagonist of H(1)-receptor. Fractions contained caffeic acid, caffeoylquinic acid and fractions contained flavonoids such as hyperin and isoquercitrin in eMMBP inhibit histamine release from mast cells, but only flavonoids such as hyperin, isoquercitrin and rutin suppress the histamine-induced contraction in guinea pig ileum. Moreover, the histamine-induced contraction was not affected by caffeic acid, however, such contraction was significantly inhibited by rutin. These results suggest that the primary antagonists of H(1)- receptor are different from the components in eMMBP that inhibit histamine release, and that these components participate in the anti-allergic activity of eMMBP.

Protease-dependent activation of nasal polyp epithelial cells by airborne fungi leads to migration of eosinophils and neutrophils

Conclusions. Proteases in fungi interact with nasal epithelial cells and enhance the production of inflammatory cytokines in vitro. These cytokines induced the migration of eosinophils and neutrophils. Protease-activated receptors (PARs) might also play a role in the process of epithelial cell activation. Objective. The nasal epithelium is the first barrier encountered by airborne allergens and an active participant in airway inflammation. Fungi have been increasingly recognized as important pathogens in sinusitis and consist of several allergenic proteins. Materials and methods. Nasal polyp epithelial cells were obtained from patients and stimulated with Alternaria, Aspergillus, and Cladosporium. Interleukin-8 (IL-8), granulocyte-macrophage colony stimulating factor (GM-CSF), and regulated on activation normal T expressed and secreted (RANTES) were measured to determine the activation of epithelial cells. Reverse transcriptase-polymerase chain reaction test (RT-PCR) for PAR mRNA expression in nasal epithelial cells was performed. Eosinophil and neutrophil migration was induced with nasal polyp epithelial cells conditioned media (HPECM). Results. Fungi enhanced the production of chemical mediators from nasal epithelial cells. When nasal epithelial cells were activated with fungi, PAR2 and PAR3 mRNAs were more strongly expressed than in nonactivated cells. Eosinophil migration was induced by RANTES and eotaxin, and neutrophil migration was induced by IL-8 in HPECM.

Effects of wogonin, wogonoside, and 3,5,7,2′,6′-pentahydroxyflavone on chemical mediator production in peritoneal exduate cells and immunoglobulin E of rat mesenteric lymph node lymphocytes

Wogonin (WG), wogonoside (WGS), and 3,5,7,2′,6′-pentahydroxyl flavanone (PHF) were isolated from Scutellaria baicalensis, and their effects on histamine, leukotriene B 4 (LTB 4), and immunoglobulin E (IgE) were examined in rats, observing for a manifestation of a type I allergic reaction. WG and WGS in the amounts of 10 and 100 μM were shown to markedly inhibit histamine release in cells stimulated with calcium ionophore A23187 or compound 48/80. PHF exerted inhibitory activity only at 100 μM. In the case of LTB 4, WG, WGS and PHF markedly inhibited LTB 4 production at the concentration of 100 μM. We also find that the increase in the IgE content induced by concanavalin A (ConA) was alleviated in the presence WG and WGS, while the inhibitory effect of PHF was much weaker. However, the magnitude of inhibitory effect observed on the content of lipid peroxidation induced by ConA was in order of PHF>WG>WGS, with PHF being the strongest. Interestingly, WG and WGS with the methoxyl group strongly inhibited histamine and IgE production, whereas PHF with the hydroxyl group in the B ring was much stronger than WG and WGS against lipid peroxidation. Based on data, it was concluded that the flavonoid components, WG, WGS, and PHF, may block a common pathway for the release of histamine and LTB 4, and that the IgE level is responsible for the lipid peroxidation induced by ConA.

Effects of sesamin and alpha-tocopherol, individually or in combination, on the polyunsaturated fatty acid metabolism, chemical mediator production, and immunoglobulin levels in Sprague-Dawley rats.

Feeding sesamin and alpha-tocopherol in combination, both at the 0.5% dietary level, to Sprague-Dawley rats for 3 weeks resulted in a trend toward decreasing the proportion of 20:4n-6 and 22:5n-6 and increasing that of 18:2n-6 in phosphatidylcholine from various tissues, suggesting interference with the metabolism of linoleic acid. This dietary manipulation significantly reduced the production of leukotriene C4 in the lung, the splenic production of leukotriene B4, and reduction of the plasma histamine level. Simultaneous administration of sesamin and alpha-tocopherol significantly increased the production of IgA, IgG, and IgM by mesenteric lymph node lymphocytes, while the IgE level tended to be reduced. These effects were not necessarily apparent by feeding these compounds separately. Thus, sesamin and alpha-tocopherol in combination would be effective for regulating the eicosanoid production and modifying the immune function.

Effects of Sesamin andα-Tocopherol on the Production of Chemical Mediators and Immunoglobulins in Brown-Norway Rats

This study investigated the effects of sesamin and α-tocopherol on eicosanoid production and immune function in the rat. Male Brown-Norway rats, 4 weeks of age, were given either control, 0.5% sesamin, 0.5% α-tocopherol, or 0.5% sesamin plus 0.5% α-tocopherol diets for 3 weeks. When sesamin and tocopherol were given together, the proportion of 20: 4n-6 phosphatidylcholine (PC) was significantly lowered in liver and lung, while that of 18: 2n-6 and 20: 3n-6 was significantly increased in liver. Simultaneous administration of these compounds significantly reduced the production by the lung of leukotriene C4 (LTC4), but there was no effect on the splenic LTC4 production and the plasma prostaglandin E2 concentration. Sesamin and tocopherol, either separately or in combination, significantly reduced both the proportion of splenic CD4+ and CD8+ T cells, but the change in the CD4+/CD8+ ratio was not significant. The effects of sesamin and tocopherol feeding on serum levels of IgA, IgE, and IgG were not so marked...

Effect of Chitin on the Production of Chemical Mediators by Peripheral Monocytes.

To investigate the mechanisms of the many favorable properties of chitin membrane in woundhealing, human peripheral monocytes were cultured on chitin membrane or other wound dressing materials, and the chemical mediators from macrophage, including prostaglandin E2 and interleukin 1, were analyzed.These mediators were detected in the supernatants of the macrophage cultures. The chitin-induced productionof chemical mediators from macrophages was less than that induced by the other dressing materials.These results suggest that each wound dressing material has a different capability of inducing th productionof inflammatory chemical mediators by macrophages, and that the favorable properties of chitin in woundhealing might be related to its lower capability to induce localized inflammation.

Enhancement and hepatocyte-modulating effect of chemical mediators and monokines produced by hepatic macrophages in rats with induced sepsis

We investigated the production of chemical mediators by hepatic macrophages from rats with sepsis and the modulation of hepatocyte function by these hepatic macrophages. The chemical mediators we measured were superoxide (O2-), TNF, IL-1, and PGE2. Production of these mediators by hepatic macrophages from rats with sepsis was significantly increased. Furthermore, protein synthesis by cultured hepatocytes was inhibited in a co-culture system of hepatocytes and hepatic macrophages from rats with sepsis, and it was even inhibited by the supernatant of cultured hepatic macrophages from septic rats. These results demonstrate that hepatic macrophages are activated in sepsis and may play a role in inducing hepatic dysfunction in sepsis.

IS DIET IMPORTANT IN RHEUMATOID ARTHRITIS?

There is evidence from several well documented case reports that occasional patients with rheumatoid arthritis (RA) may develop aggravation of their arthritis as a result of allergy to some ingredient in the diet. A variety of foodstuffs have been implicated including milk and milk products, corn and cereals. Total fasting results in improvement in rheumatoid arthritis, but appears to be mediated by diminution in production of chemical mediators of inflammation, rather than by elimination of a dietary allergen. There is conflicting evidence from studies using various intestinal probes that patients with rheumatoid arthritis may have a 'leaky' intestinal mucosa allowing food allergens to be more easily absorbed. Clinical therapeutic trials of exclusion diets have employed the standard strategy of the double-blind randomized method. However, this presupposes that patients entered into such a study are capable of improvement with dietary manipulation. Since this is often not the case, a more appropriate method would be to employ the 'intensive research design' also known as 'single case experiment' and 'N of 1' study. 'Masked food intolerance' is an attractive hypothesis, but extremely difficult to prove. It is doubtful whether fish oils and/or evening primrose oil will be of significant long term benefit for patients with RA. However, they do provide for the possibility that a fatty acid-like substance may be found which may be incorporated into cell membranes, thereby preventing production of mediators of inflammation, such as prostaglandin E2 and leukotriene B4.

Immunological study of late cerebral vasospasm in subarachnoid hemorrhage. Detection of immunoglobulins, C3, and fibrinogen in cerebral arterial walls by immunofluorescence method

Although the occurrence of so-called late cerebral vasospasm after subarachnoid hemorrhage (SAH) due to ruptured cerebral aneurysm is well-known, its etiology still remains obscure. The authors previously reported that C1q (q-subfraction of the first complement component) binding substance, formed in blood-stained cerebrospinal fluid, might trigger the activation of the complement system in the subarachnoid space and develop cerebral vasospasm. This time, the authors investigated constricted cerebral arterial walls after SAH by immunofluorescent technique to see what immunological changes they were subject to, following the activation of the complement system and in the course of the possible production of chemical mediators (anaphylatoxin, etc.). One hundred and thirty-eight major intracranial arterial specimens obtained from patients with and without central nervous system disorders at autopsy were examined for deposits of immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM), the third complement component (C3) or fibrinogen in the arterial walls. In cases of SAH with definite or probable vasospasm, deposits of both IgG and C3 in the arterial media were observed in 74% of the arterial specimens examined. However, these deposits could not be found at all in the patients who died within 48 hours after aneurysmal rupture. The frequency of the deposits of both IgG and C3 was 42% in hypertensive intracerebral hematoma, 44% in cerebral infarction, 42% in brain tumor, 75% in meningoencephalitis. Deposits of IgA, IgM or fibrinogen were also observed in the media, but with much less frequency than those of IgG or C3 in all cases. The significance of deposits of IgG and C3 in the media found in cases with late vasospasm after SAH is unclear at present, but it is thought that they represent an antibody to degenerated arterial smooth muscles due to constriction and complement bound to the antibody. In other words, it is highly likely that those deposits indicate arteritis or an inflammatory process in the arterial wall.

Migration Inhibitory Activity in Serum and Cell Supernatants in Patients with Sezary Syndrome

The abnormal lymphocytes from patients with the Sezary syndrome produce macrophage migration inhibitory factors (MIF) both in vitro and in vivo. Five of six individuals studied had significant serum MIF activity and one had borderline activity. In contrast, in this study 47 normal individuals and 9 of 10 patients with extensive skin disease other than that of the Sezary syndrome had no such activity. Since the neoplastic T cells in patients with the Sezary syndrome localize in the skin, their production of chemical mediators in that site may be responsible for the generalized exfoliative erythroderma seen in that disease.

Antiinflammatory activity of vitamin E.

By systemic administration of vitamin E, studies were made to see whether dextran edema in rabbits and histamine and acetylcholine reactions in human can be depressed. Also, whether its topical administration can attain the suppression of croton oil dermatitis in rabbits and human plaster dermatitis was examined. It was found that vitamin E had antiinflammatory action, especially an action to suppress the enlargement and severity of the inflammation. The effect of such action of vitamin E was thought to be due to inhibition action of vitamin E on liberation and production of chemical mediators, as a result of stabilization action of vitamin E on the membranes although some reservations have been made on the supporting factor that vitamin E may contribute to antispreading factor and suppressive action on acceleration of capillary permeability.