Oxidative stress and inflammatory mediators contribute to endothelial dysfunction in high-fat diet-induced obesity in mice

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Signaling pathways associated with the expression of inflammatory mediators activated during the course of two models of experimental periodontitis

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Spatial expression of two anti-inflammatory mediators, annexin 1 and galectin-1, in nasal polyposis

Background There is renewed interest in the role played by specific counter-regulatory mechanisms to control the inflammatory host response, poorly investigated in human pathology. Here, we monitored the expression of two anti-inflammatory mediators, annexin 1 and galectin-1, and assessed their potential link to glucocorticoids' (GCs) effective control of nasal polyposis (NP).Methods Total patterns of mRNA and protein expression were analysed by quantitative real-time PCR (qPCR) and Western blotting analyses, whereas ultrastructural immunocytochemistry was used for spatial localization and quantification of each mediator, focusing on mast cells, eosinophils and epithelial cells.Results Up-regulation of the annexin 1 gene, and down-regulation of galectin-1 gene, was detected in polypoid tissue compared with nasal mucosa. Patient treatment with betamethasone augmented galectin-1 protein expression in polyps. At the cellular level, control mast cells and eosinophils displayed higher annexin 1 expression, whereas marked galectin-1 immunolabelling was detected in the granule matrix of mast cells. Cells of glandular duct epithelium also displayed expression of both annexin 1 and galectin-1, augmented after treatment.Conclusion Mast cells and epithelial cells appeared to be pivotal cell types involved in the expression of both annexin 1 and galectin-1. It is possible that annexin 1 and galectin-1 could be functionally associated with a specific mechanism in NP and that GC exert at least part of their beneficial effects on the airway mucosa by up-regulating, in a specific cell target fashion, these anti-inflammatory agonists.

Role of inflammatory mediators in priming, activation, and deformability of bovine neutrophils

Objective-To determine the capacity of inflammatory mediators tumor necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), platelet-activating factor (PAF), lipopolysaccharide (LPS), and leukotoxin to prime, activate, or alter deformability of adult bovine neutrophils.Sample Population-Blood collected from 5 healthy adult Holstein cows.Procedure-Isolated neutrophils or whole brood was incubated with TNF-alpha, IL-8, PAF, LPS, or leukotoxin, and neutrophil chemiluminescence, degranulation, deformability, shape change, CD11b expression, and size distribution was measured.Results-incubation with TNF-alpha, IL-8; PAF, and IFS primed neutrophils for oxygen radical release but caused minimal oxygen radical release by themselves. None of the inflammatory mediators induced degranulation. Incubation with TNF-alpha and PAF resulted in a decrease in neutrophil deformability and induced shape change in neutrophils. incubation with PAF consistently resulted in an increase in neutrophil size as measured by use of flow cytometry. Only IL-8 caused an increase in expression of CD11b by neutrophils.Conclusions and Clinical Relevance-Inflammatory mediators tested had minimal effects on neutrophil oxygen radical production or degranulation but did prime neutrophils for oxygen radical production. Incubation with PAF and TNF-alpha caused a decrease in neutrophil deformability and altered neutrophil shape and size. Results of our study indicate that PAF- and TNF-alpha-induced changes in neutrophil deformability and size may cause integrin- and setectin-independent trapping of neutrophils in the lungs of cattle with pneumonic pasteurellosis.

Female sex hormones mediate the allergic lung reaction by regulating the release of inflammatory mediators and the expression of lung E-selectin in rats

Background: Fluctuations of estradiol and progesterone levels caused by the menstrual cycle worsen asthma symptoms. Conflicting data are reported in literature regarding pro and anti-inflammatory properties of estradiol and progesterone.Methods: Female Wistar rats were ovalbumin (OVA) sensitized 1 day after resection of the ovaries (OVx). Control group consisted of sensitized-rats with intact ovaries (Sham-OVx). Allergic challenge was performed by aerosol (OVA 1%, 15 min) two weeks later. Twenty four hours after challenge, BAL, bone marrow and total blood cells were counted. Lung tissues were used as explants, for expontaneous cytokine secretion in vitro or for immunostaining of E-selectin.Results: We observed an exacerbated cell recruitment into the lungs of OVx rats, reduced blood leukocytes counting and increased the number of bone marrow cells. Estradiol-treated OVx allergic rats reduced, and those treated with progesterone increased, respectively, the number of cells in the BAL and bone marrow. Lungs of OVx allergic rats significantly increased the E-selectin expression, an effect prevented by estradiol but not by progesterone treatment. Systemically, estradiol treatment increased the number of peripheral blood leukocytes in OVx allergic rats when compared to non treated-OVx allergic rats. Cultured-BAL cells of OVx allergic rats released elevated amounts of LTB4 and nitrites while bone marrow cells increased the release of TNF-α and nitrites. Estradiol treatment of OVx allergic rats was associated with a decreased release of TNF-α, IL-10, LTB4 and nitrites by bone marrow cells incubates. In contrast, estradiol caused an increase in IL-10 and NO release by cultured-BAL cells. Progesterone significantly increased TNF- α by cultured BAL cells and bone marrow cells.Conclusions: Data presented here suggest that upon hormonal oscillations the immune sensitization might trigger an allergic lung inflammation whose phenotype is under control of estradiol. Our data could contribute to the understanding of the protective role of estradiol in some cases of asthma symptoms in fertile ans post-menopausal women clinically observed. © 2010 de Oliveira et al; licensee BioMed Central Ltd.

Signaling Pathways Activation by Primary Endodontic Infectious Contents and Production of Inflammatory Mediators

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Biocompatibility of New Calcium Aluminate Cement: Tissue Reaction and Expression of Inflammatory Mediators and Cytokines

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Anti-Inflammatory Effects of Low-Level Light Emitting Diode Therapy on Achilles Tendinitis in Rats

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Evaluation of the anti-inflammatory, analgesic and antipyretic activities of the natural polyphenol chlorogenic acid

Phenolic compounds are numerous and ubiquitous in the plant kingdom, being particularly present in health-promoting foods. Epidemiological evidences suggest that the consumption of polyphenol-rich foods reduces the incidence of cancer, coronary heart disease and inflammation. Chlorogenic acid (CGA) is one of the most abundant polyphenol compounds in human diet. Data obtained from in vivo and in vitro experiments show that CGA mostly presents antioxidant and anti-carcinogenic activities. However, the effects of CGA on the inflammatory reaction and on the related pain and fever processes have been explored less so far. Therefore, this study was designed to evaluate the anti-inflammatory, antinociceptive and antipyretic activities of CGA in rats. In comparison to control, CGA at doses 50 and 100 mg/kg inhibited carrageenin-induced paw edema beginning at the 2nd hour of the experimental procedure. Furthermore, at doses 50 and 100 mg/kg CGA also inhibited the number of flinches in the late phase of formalin-induced pain test. Such activities may be derived from the inhibitory action of CGA in the peripheral synthesis/release of inflammatory mediators involved in these responses. On the other hand, even at the highest tested dose (200 mg/kg), CGA did not inhibit the febrile response induced by lipopolysaccharide (LPS) in rats. Additional experiments are necessary in order to clarify the true target for the anti-inflammatory and analgesic effects of CGA. © 2006 Pharmaceutical Society of Japan.

Anti-inflammatory activity of Lychnophora passerina, Asteraceae (Brazilian arnica)

Ethnopharmacological relevance: Lychnophora passerina (Asteraceae), popularly known as arnica, is used to treat inflammation, pain, rheumatism, contusions, bruises and insect bites in Brazilian traditional medicine. Materials and methods: The anti-inflammatory activity of crude ethanolic extract of aerial parts of L. passerina and its ethyl acetate and methanolic fractions had their abilities to modulate the production of NO, TNF-α and IL-10 inflammatory mediators in LPS/IFN-γ-stimulated J774.A1 macrophages evaluated. Moreover, the crude ethanolic extract and derived fractions were also in vivo assayed by carrageenan-induced paw oedema in mice. Results: In vitro assays showed remarkable anti-inflammatory activity of L. passerina crude ethanolic extract (EE) and its ethyl acetate (A) and methanolic (M) fractions, through the inhibition of production of NO and TNF-α inflammatory mediators and induction of production of IL-10 anti-inflammatory cytokine. In vivo assays showed anti-inflammatory activity for EE 10% ointment, similar to the standard drug diclofenac gel. The A and M fraction ointments 20% presented anti-inflammatory activity. Conclusion: The results obtained showed that possible anti-inflammatory effects of EE and its A and M fractions may be attributed to inhibition pro-inflammatory cytokines production, TNF-α and NO and to increased IL-10 production. EE, A and M ointments showed topical in vivo anti-inflammatory activity. The in vivo anti-inflammatory activity of EE of L. passerina may be related to synergistic effects of different substances in the crude extract. Therefore, traditional use of aerial parts of L. passerina in the inflammatory conditions could be beneficial to treat topical inflammatory conditions, as evidenced by the present study. © 2011 Elsevier B.V. All rights reserved.

Functional activity of neutrophils and systemic inflammatory response of Down's syndrome patients with periodontal disease

Periodontal disease (PD) is characterized as an inflammatory process that compromises the support and protection of the periodontium. Patients with Down's syndrome (DS) are prone to develop PD. Neutrophils (NE) are the first line of defense against infection and their absence sets the stage for disease. Aim: To compare the activity and function of NE in the peripheral blood from DS patients with and without PD, assisted at the Center for Dental Assistance to Patients with Special Needs affiliated with the School of Dentistry of Araçatuba, Brazil. Methods: Purified NE were collected from peripheral blood of 22 DS patients. NE were used to detect the 5-lypoxigenase (5-LO) expression by RT-PCR. Plasma from peripheral blood was collected to measure tumor necrosis factor-a (TNF-α) and interleukin-8 (IL-8) by ELISA and nitrite (NO 3) using a Griess assay. Results: Data analysis demonstrated that DS patients with PD present high levels of TNF-a and IL-8 when compared with DS patients without PD. However, there was no statistically significant difference in the levels of NO 3 production between the groups. The levels of the inflammatory mediator 5-LO expression increased in DS patients with PD. Conclusions: According with these results, it was concluded that TNF-α and IL-8 are produced by DS patients with PD. Furthermore, DS patients with PD presented high levels of 5-LO expression, suggesting the presence of leukotriene B 4 (LTB 4) in PD, thus demonstrating that the changes in NE function due to the elevation of inflammatory mediators contribute to PD.

Anti-inflammatory mechanisms of the annexin A1 protein and its mimetic peptide Ac2-26 in models of ocular inflammation in vivo and in vitro

Annexin A1 (AnxA1) is a protein that displays potent anti-inflammatory properties, but its expression in eye tissue and its role in ocular inflammatory diseases have not been well studied. We investigated the mechanism of action and potential uses of AnxA1 and its mimetic peptide (Ac2-26) in the endotoxin-induced uveitis (EIU) rodent model and in human ARPE-19 cells activated by LPS. In rats, analysis of untreated EIU after 24 and 48 h or EIU treated with topical applications or with a single s.c. injection of Ac2-26 revealed the anti-inflammatory actions of Ac2-26 on leukocyte infiltration and on the release of inflammatory mediators; the systemic administration of Boc2, a formylated peptide receptor (fpr) antagonist, abrogated the peptide's protective effects. Moreover, AnxA1-/- mice exhibited exacerbated EIU compared with wild-type animals. Immunohistochemical studies of ocular tissue showed a specific AnxA1 posttranslational modification in EIU and indicated that the fpr2 receptor mediated the anti-inflammatory actions of AnxA1. In vitro studies confirmed the roles of AnxA1 and fpr2 and the protective effects of Ac2-26 on the release of chemical mediators in ARPE-19 cells. Molecular analysis of NF-κB translocation and IL-6, IL-8, and cyclooxygenase-2 gene expression indicated that the protective effects of AnxA1 occur independently of the NF-κB signaling pathway and possibly in a posttranscriptional manner. Together, our data highlight the role of AnxA1 in ocular inflammation, especially uveitis, and suggest the use of AnxA1 or its mimetic peptide Ac2-26 as a therapeutic approach. Copyright © 2013 by The American Association of Immunologists, Inc.

Green tea polyphenol epigallocatechin-3-gallate and cranberry proanthocyanidins act in synergy with cathelicidin (LL-37) to reduce the LPS-induced inflammatory response in a three-dimensional co-culture model of gingival epithelial cells and fibroblasts

Objectives: The human antimicrobial peptide cathelicidin (LL-37) possesses anti-inflammatory properties that may contribute to attenuating the inflammatory process associated with chronic periodontitis. Plant polyphenols, including those from cranberry and green tea, have been reported to reduce inflammatory cytokine secretion by host cells. In the present study, we hypothesized that A-type cranberry proanthocyanidins (AC-PACs) and green tea epigallocatechin-3-gallate (EGCG) act in synergy with LL-37 to reduce the secretion of inflammatory mediators by oral mucosal cells. Methods: A three-dimensional (3D) co-culture model of gingival epithelial cells and fibroblasts treated with non-cytotoxic concentrations of AC-PACs (25 and 50 mg/ml), EGCG (1 and 5 mg/ml), and LL-37 (0.1 and 0.2 mM) individually and in combination (AC-PACs + LL-37 and EGCG + LL-37) were stimulated with Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS). Multiplex ELISA assays were used to quantify the secretion of 54 host factors, including chemokines, cytokines, growth factors, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs). Results: LL-37, AC-PACs, and EGCG, individually or in combination, had no effect on the regulation of MMP and TIMP secretion but inhibited the secretion of several cytokines. ACPACs and LL-37 acted in synergy to reduce the secretion of CXC-chemokine ligand 1 (GRO-a), granulocyte colony-stimulating factor (G-CSF), and interleukin-6 (IL-6), and had an additive effect on reducing the secretion of interleukin-8 (IL-8), interferon-g inducible protein 10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1) in response to LPS stimulation. EGCG and LL-37 acted in synergy to reduce the secretion of GRO-a, G-CSF, IL-6, IL-8, and IP-10, and had an additive effect on MCP-1 secretion. Conclusion: The combination of LL-37 and natural polyphenols from cranberry and green tea acted in synergy to reduce the secretion of several cytokines by an LPS-stimulated 3D coculture model of oral mucosal cells. Such combinations show promising results as potential adjunctive therapies for treating inflammatory periodontitis.

Experimental evidence of heparanase, Hsp70 and NF-κB gene expression on the response of anti-inflammatory drugs in TNBS-induced colonic inflammation

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