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1.
Alain Stricker-Krongrad Catherine Shoemake Miao Zhong Jason Liu Guy Bouchard 《BMC clinical pathology》2018,18(1):1
Background
Measuring expression profiles of inflammatory biomarkers is important in monitoring the polarization of immune responses; therefore, results should be independent of quantitation methods if they are to be accepted as validated clinical pathology biomarkers. To evaluate effects of differing quantitation methods, the seven major circulating Th1/Th2/Th17 cytokines interleukin 2 (IL-2), interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), IL-4, IL-6, IL-10 and IL-17A were quantified in plasma of lipopolysaccharide (LPS)-treated mice with two different multiplex platforms.Methods
Female C57BL6 mice were treated orally with vehicle or dexamethasone, followed by LPS intravenously. Plasma samples were analyzed 0.5, 1, 2, 4, and 6 h post-LPS challenge with assays at Myriad-RBM and compared to assays performed on a BD Accuri C6 flow cytometer.Results
IL-17A response to LPS was limited but sustained, and the response for the remaining cytokines were early and transient; dexamethasone reduced expression of all 7 cytokines. TNF-α and IL-6 levels were similar across both assays, and IL-4 levels were generally very low. Plasma levels of remaining cytokines were variably lower with BD assays than Myriad-RBM assays.Conclusions
The present findings demonstrate that quantitation of circulating biomarkers of inflammation can be achieved using multiplexed flow cytometry, but careful consideration must be taken for assay validation when cross-referencing with another multiplexed assay.2.
Karolina Bień Magdalena Żmigrodzka Piotr Orłowski Aleksandra Fruba Łukasz Szymański Wanda Stankiewicz Zuzanna Nowak Tadeusz Malewski Małgorzata Krzyżowska 《Inflammation research》2017,66(8):679-690
Objective and design
The aim of this study was to elucidate the role of apoptosis mediated through Fas/FasL pathway using the mouse model of atopic dermatitis (AD).Materials and treatment
AD was induced by epicutaneous application of ovalbumin (OVA) in wild-type C57BL/6, B6. MRL-Faslpr/J (Fas?) and B6Smn.C3-Faslgld/J (FasL?) mouse strains.Methods
Skin samples were subjected to staining for Fas/FasL expression, M30 epitope and assessment of inflammatory response via immunohistochemical staining. Cytokine and chemokine production was assessed by real-time PCR.Results
In comparison to wild-type mice, OVA sensitization of Fas- and FasL-deficient mice led to increased epidermal and dermal thickness, collagen deposition and local inflammation consisting of macrophages, neutrophils and CD4+?T cells. Fas- and FasL-deficient mice showed increased total counts of regulatory T cells (Tregs) and IgE levels in blood as well as increased expression of IL-1β, IL-4, IL-5, IL-13 and TGF-1β mRNA in comparison to wild-type mice. On the other hand, expression of CXCL9 and CXCL10, IL-17 mRNAs in the skin samples in Fas- and FasL-deficient mice was decreased.Conclusions
Our results show that lack of the Fas-induced apoptosis leads to exacerbation of AD characteristics such as Th2 inflammation and dermal thickening. Therefore, Fas receptor can play an important role in AD pathogenesis by controlling development of the local inflammation.3.
José Guilherme F. M. Galvão Luiz Henrique Agra Cavalcante-Silva Deyse Cristina M. Carvalho Laércia Karla D. P. Ferreira Talissa Mozzini Monteiro Adriano Francisco Alves Larissa Adilis M. P. Ferreira Francisco Allysson A. F. Gadelha Marcia Regina Piuvezam Sandra Rodrigues-Mascarenhas 《Inflammation research》2017,66(12):1117-1130
Purpose
Ouabain, an Na+/K+-ATPase inhibitor hormone, presents immunomodulatory actions, including anti-inflammatory effect on acute inflammation models.Methods
In the present study, the effect of ouabain in a model of allergic airway inflammation induced by ovalbumin (OVA) was assessed.Results
Initially, it was observed that ouabain treatment inhibited cellular migration induced by OVA on bronchoalveolar lavage fluid (BALF), mostly granulocytes, without modulating macrophage migration. In addition, it was observed, by flow cytometry, that ouabain reduces CD3high lymphocytes cells on BALF. Furthermore, treatment with ouabain decreased IL-4 and IL-13 levels on BALF. Ouabain also promoted pulmonary histological alterations, including decreased cell migration into peribronchiolar and perivascular areas, and reduced mucus production in bronchioles regions observed through hematoxylin–eosin (HE) and by periodic acid-Schiff stain, respectively. Allergic airway inflammation is characterized by high OVA-specific IgE serum titer. This parameter was also reduced by the treatment with ouabain.Conclusions
Therefore, our data demonstrate that ouabain negatively modulates allergic airway inflammation induced by OVA.4.
Background
Astragali radix Antiasthmatic Decoction (AAD), a traditional Chinese medication, is found effective in treating allergic diseases and chronic cough. The purpose of this study is to determine whether this medication could suppress allergen-induced airway hyperresponsiveness (AHR) and remodeling in mice, and its possible mechanisms.Methods
A mouse model of chronic asthma was used to investigate the effects of AAD on the airway lesions. Mice were sensitized and challenged with ovalbumin (OVA), and the extent of AHR and airway remodeling were characterized. Cells and cytokines in the bronchoalveolar lavage fluid (BALF) were examined.Results
AAD treatment effectively decreased OVA-induced AHR, eosinophilic airway inflammation, and collagen deposition around the airway. It significantly reduced the levels of IL-13 and TGF-β1, but exerted inconsiderable effect on INF-γ and IL-10.Conclusions
AAD greatly improves the symptoms of allergic airway remodeling probably through inhibition of Th2 cytokines and TGF-β1.5.
Yequan Huang Weiwei Qiao Xinhuan Wang Qian Gao Yao Peng Zhuan Bian Liuyan Meng 《Inflammation research》2018,67(9):777-788
Aim
The study aimed to investigate the effects of DNA repair proteins on cell apoptosis in human DPSCs during inflammation.Methods
Lipopolysaccharide (LPS) was used to stimulate inflammation in dental pulp in vivo and in vitro. We identified the activation of DSB response and DNA repair proteins in inflamed pulp tissue and in LPS-treated human DPSCs. Then we transfected the cells with Ku70 (a key protein involved in NHEJ) siRNA and detected the expression changes of γ-H2A.X, DNA repair proteins and cell apoptosis.Results
Immunohistochemical staining showed that at 4 and 6 days of pulpitis the expression of Ku70 and γ-H2A.X significantly increased. The levels of γ-H2A.X, Ku70, Xrcc4, and Rad51 increased considerably in the LPS-treated DPSCs. Furthermore, decreased expression of Ku70 could increase the number of γ-H2A.X foci, apoptotic cells and reduce cell viability in DPSCs.Conclusions
The results indicate that NHEJ pathway was the main mechanism involved in DNA damage response induced by repeated LPS stimulation in DPSCs. Meanwhile, the findings suggested that Ku70 serves importantly in the apoptosis of DPSCs in the inflammatory environment.6.
Mingcheng Huang Lihui Wang Shan Zeng Qian Qiu Yaoyao Zou Maohua Shi Hanshi Xu Liuqin Liang 《Inflammation research》2017,66(5):433-440
Objectives
To evaluate the inhibition of indirubin in FLSs migration, invasion, activation, and proliferation in RA FLSs.Methods
The levels of IL-6 and IL-8 in cultural supernatants were measured by ELISA. RA FLS migration and invasion in vitro were measured by the Boyden chamber method and the scratch assay. Signal transduction protein expression was measured by western blot. FLS proliferation was detected by Edu incorporation. F-actin was measured by immunofluorescence staining.Results
We found that indirubin reduced migration, invasion, inflammation, and proliferation in RA FLSs. In addition, we demonstrated that indirubin inhibited lamellipodium formation during cell migration. To gain insight into molecular mechanisms, we evaluated the effect of indirubin on PAK1 and MAPK activation. Our results indicated that indirubin inhibited the activity of PAK1 and MAPK.Conclusions
Our observations suggest that indirubin may be protective against joint destruction in RA by regulating synoviocyte migration, invasion, activation, and proliferation.7.
Alessandra Mileni Versuti Ritter Luzmarina Hernandes Bruno Ambrosio da Rocha Camila Fernanda Estevão-Silva Edirlene Sara Wisniewski-Rebecca Joice dos Santos Cezar Silvana Martins Caparroz-Assef Roberto Kenji Nakamura Cuman Ciomar Aparecida Bersani-Amado 《Inflammation research》2017,66(8):725-737
Aim
This study evaluated whether anethole attenuates the inflammatory response and joint damage in a model of adjuvant-induced arthritis (AIA) in rats.Methods
The animals were treated with 62.5-, 125-, or 250-mg/kg anethole daily for 21 days after AIA and necropsied on days 14 and 21 to evaluate the number of serum and synovial leukocytes (total and differential), serum cytokines (IL-2, IL-6, IL-12, IL-17, and TNF-α), and nitric oxide concentrations. Morphologic changes in the cartilage and bone of the femorotibial articulation in both left paw and right paw were studied in hematoxylin/eosin and Sirius Red-hematoxylin sections.Results
Different doses of anethole suppressed paw swelling and the number of serum and synovial leukocytes. However, 250 mg/kg of anethole more effectively controlled local and systemic inflammation. Histological evaluation revealed significant prevention of cartilage damage and inflammatory infiltrate scores. Morphometric analysis showed pannus formation, the thickness of the articular cartilage, and bone resorption lower in the anethole-treated AIA group compared to untreated AIA group on both days 14 and 21. These significant anti-inflammatory effects in the anethole-treated AIA group were associated with downregulation of cytokines and nitric oxide levels.Conclusion
Therefore, anethole may be a useful intervention to treat inflammatory arthritis.8.
Purpose of Review
We aim to provide an in-depth review of recent literature highlighting the role of inflammation involving the adipose tissue, liver, skeletal muscles, and gastrointestinal tract in the development of metabolic complications among persons living with HIV (PLWH).Recent Findings
Recent studies in PLWH have demonstrated a significant association between circulating inflammatory markers and development of insulin resistance and metabolic complications. In adipose tissue, pro-inflammatory cytokine expression inhibits adipocyte insulin signaling, which alters lipid and glucose homeostasis. Increased lipolysis and lipogenesis elevate levels of circulating free fatty acids and promote ectopic fat deposition in liver and skeletal muscles. This leads to lipotoxicity characterized by a pro-inflammatory response with worsening insulin resistance. Finally, HIV is associated with gastrointestinal tract inflammation and changes in the gut microbiome resulting in reduced diversity, which is an additional risk factor for diabetes.Summary
Metabolic complications in PLWH are in part due to chronic, multisite tissue inflammation resulting in dysregulation of glucose and lipid trafficking, utilization, and storage.9.
Yohei Yamaguchi Tomoko Kurita-Ochiai Ryoki Kobayashi Toshihiko Suzuki Tomohiro Ando 《Inflammation research》2017,66(1):59-65
Objective
Porphyromonas gingivalis is involved in the pathogenesis of chronic inflammatory periodontal disease. Recent studies have suggested that the NLRP3 inflammasome plays an important role in the development of chronic inflammation. We investigated a possible association between the inflammasome in gingival inflammation and bone loss induced by P. gingivalis infection using NLRP3-deficient mice.Methods
Wild-type and NLRP3-deficient mice were injected orally with P. gingivalis. We assessed alveolar bone loss, expression of pro-interleukin (IL)-1β, pro-IL-18, receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin (OPG) in gingival tissue, as well as IL-1β, IL-18, and IL-6 production and caspase-1 activity in peritoneal macrophages.Results
Porphyromonas gingivalis challenge significantly increased alveolar bone loss; gingival gene expression of pro-IL-1β, pro-IL-18, and RANKL; production of IL-1β, IL-18, and IL-6; and caspase-1 activity in peritoneal macrophages of wild-type mice, but did not affect NLRP3-deficient mice. Meanwhile, OPG mRNA expression in gingival tissue and peritoneal IL-6 production were significantly higher in NLRP3-knockout mice.Conclusions
Porphyromonas gingivalis activated innate immune cells via the NLRP3 inflammasome. These results suggest that the NLRP3 inflammasome, followed by a response from the IL-1 family, is critical in periodontal disease induced by wild-type P. gingivalis challenge via sustained inflammation.10.
Yi-Ju Pan Wei-Hsun Wang Tzu-Yao Huang Wei-Hsiang Weng Chun-Kai Fang Yu-Chan Chen Jeng-Jong Hwang 《Inflammation research》2018,67(10):847-861
Objective and design
To investigate the amelioration effects of quetiapine on rheumatoid arthritis with RAW 264.7 macrophage and collagen-induced arthritis (CIA) DBA/1J mouse model.Subjects
RAW 264.7 macrophage and DBA/1J mice.Treatment
Lipopolysaccharide and collagen.Methods
RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS) followed by quetiapine treatments were investigated. Activations of CD80 and CD86 were analyzed by flow cytometry. Pro-inflammatory cytokines such as IL-6, TNF-α and IL-1β were analyzed by ELISA. Proteins involved in signaling pathways related to the formation of rheumatoid arthritis were assayed by Western blotting. Therapeutic efficacy of quetiapine in CIA mouse model was also assayed. 18F-FDG/micro-PET was used to monitor the inflammation status in the joints, and the severity of bone erosion was evaluated with micro-CT and H&E staining.Results
The inhibition of pro-inflammatory cytokines by quetiapine was found through the ERK and AKT phosphorylation and subsequent NF-κB and CREB signaling pathways. Pro-inflammatory cytokines such as IL-17, IL-6 and IL-1β were decreased, while immunosuppressive factors such as TGF-β and IL-10 were increased in CIA mice treated with quetiapine. Notably, no uptake of 18F-FDG and bone erosion was found with micro-PET images on days 32 and 43 in the quetiapine-treated and normal control groups. However, significant uptake of 18F-FDG could be observed in the CIA group during the same time course. Similar results were further verified with ex vivo autoradiography.Conclusion
Taken together, these results suggest that quetiapine is a potential anti-inflammatory drug, and may be used as an adjuvant for the treatment of rheumatoid arthritis.11.
Objective and design
Arthritic gout is caused by joint inflammation triggered by the damaging effects of monosodium uric acid (MSU) crystal accumulation in the synovial space. Neutrophils play a major role in mediating joint inflammation in gout. Along with neutrophils, other immune cells, such as macrophages, are present in inflamed joints and contribute to gout pathogenesis. Neutrophils form neutrophil extracellular traps (NETs) in response to MSU crystals. In the presence of MSU crystals, macrophages release IL-1β, a cytokine crucial to initiate gout pathogenesis and neutrophil recruitment. Our research investigated interactions between human macrophages and neutrophils in an in vitro model system and asked how macrophages affect NET formation stimulated by MSU crystals.Materials or subjects
Human neutrophils and PBMCs were isolated from peripheral blood of healthy volunteers. PBMCs were differentiated into macrophages in vitro using human M-CSF.Treatment
Human neutrophils were pretreated with macrophage-conditioned media, neutrophil-conditioned media, recombinant human IL-1β or anakinra prior to stimulation by MSU crystals.Method
Interaction of neutrophils with MSU crystals was evaluated by live imaging using confocal microscopy. The presence of myeloperoxidase (MPO) and neutrophil elastase (NE) was measured by ELISA. NET formation was quantitated by Sytox Orange-based extracellular DNA release assay and NE-DNA ELISA. AggNET formation was assessed by macroscopic evaluation.Results
We found that crystal- and cell-free supernatants of macrophages stimulated with MSU crystals promote MSU crystal-stimulated NET formation in human neutrophils. This observation was confirmed by additional assays measuring the release of MPO, NE, and the enzymatic activity of NE. MSU crystal-induced NET formation remained unchanged when neutrophil supernatants were tested. IL-1β is a crucial cytokine orchestrating the onset of inflammation in gout and is known to be released in large amounts from macrophages following MSU crystal stimulation. We found that recombinant IL-1β strongly promoted MSU crystal-induced NET formation in human neutrophils. Interestingly, IL-1β alone did not induce any NET release. We also found that clinical grade anakinra, an IL-1 receptor blocker, strongly reduced the NETosis-enhancing effect of macrophage supernatants indicating that IL-1β is mainly responsible for this effect.Conclusions
Macrophage-derived IL-1β enhances MSU crystal-induced NET release in neutrophils. We identified a new mechanism by which macrophages and IL-1β affect neutrophil functions, and could contribute to the inflammatory conditions present in gout. Our results also revealed a new anti-inflammatory mechanism of anakinra.12.
Kelsey H. Collins Walter Herzog Raylene A. Reimer Carol R. Reno Bryan J. Heard David A. Hart 《Inflammation research》2018,67(2):139-146
Objective and design
The purpose of this study was to investigate if diet-induced obesity (DIO) and subsequent low-level systemic inflammation would result in local increases in pro-inflammatory mediators in the vitreous humour (VH) of the eyes of rats.Methods
Sixteen male Sprague–Dawley rats were fed a high-fat/high-sucrose (n?=?9) or chow control-diet (n?=?7) for 12-weeks. RT-qPCR was conducted on RNA from VH cells and a 27-plex Luminex® Assay was conducted on VH fluid and serum.Results
Increased protein levels for IL-1β, IL-6, and IL-18 in both serum and VH fluid were observed. VH protein levels for IL-13 and IL-17 were also increased. All mediators significantly increased in VH fluid were also positively correlated with percent body fat. Increased mRNA levels in VH cells for an oxidative stress molecule were accompanied by decreased mRNA levels for an antioxidant scavenger, suggesting an antioxidant/oxidant imbalance in the VH with DIO. In addition, decreased mRNA levels for TRAIL, FAS-L and TGF-β, molecules associated with immune privilege, were also significantly depressed.Conclusions
DIO-related metabolic disturbances disrupt VH homeostasis in a manner that reflects development of a pro-inflammatory environment. Prolonged exposure to such an environment may lead to overt pathologies with compromised eye function.13.
Guoying Ni Zaowen Liao Shu Chen Tianfang Wang Jianwei Yuan Xuan Pan Kate Mounsey Shelley Cavezza Xiaosong Liu Ming Q. Wei 《BMC immunology》2017,18(1):40
Background
Cancer therapeutic vaccine induced cytotoxic T cell (CTL) responses are pivotal for the killing of tumour cells. Blocking interleukin 10 (IL-10) signalling at the time of immunization increases vaccine induced CTL responses and improves prevention of tumour growth in animal models compared to immunization without an IL-10 signalling blockade. Therefore, this immunization strategy may have potential to curtail cancer in a clinical setting. However, IL-10 deficiency leads to autoimmune disease in the gut. Blocking IL-10 at the time of immunization may result in unwanted side effects, especially immune-pathological diseases in the intestine.Methods
We investigated whether blocking IL-10 at the time of immunization results in intestinal inflammation responses in a mouse TC-1 tumour model and in a NOD autoimmune disease prone mouse model.Results
We now show that blocking IL-10 at the time of immunization increases IL-10 production by CD4+ T cells in the spleen and draining lymph nodes, and does not result in blood cell infiltration to the intestines leading to intestinal pathological changes. Moreover, immunization with papillomavirus like particles combined with simultaneously blocking IL-10 signalling does not increase the incidence of autoimmune disease in Non-obese diabetic (NOD) mice.Conclusions
Our results indicate that immunization with an IL-10 inhibitor may facilitate the generation of safe, effective therapeutic vaccines against chronic viral infection and cancer.14.
Connor Stevenson Di Jiang Niccolette Schaefer Yoko Ito Reena Berman Amelia Sanchez Hong Wei Chu 《Inflammation research》2017,66(8):691-700
Objective
To evaluate the effects of MUC18 on IL-13-mediated airway inflammatory responses in human airway epithelial cells and in mice.Materials
Primary normal human tracheobronchial epithelial (HTBE) cells, wild-type (WT) and Muc18 knockout (KO) mice, and mouse tracheal epithelial cells (mTECs) were utilized.Treatment
Cultured HTBE cells treated with MUC18 siRNA or MUC18 expressing lentivirus were incubated with IL-13 (10 ng/mL) for 24 h. Mice were intranasally instilled with 500 ng of IL-13 for 3 days. mTECs were treated with IL-13 (10 ng/mL) for 3 days.Methods
PCR was used to measure mRNA expression. Western Blot and ELISAs were used to quantify protein expression. Cytospins of bronchoalveolar lavage (BAL) cells were used to obtain leukocyte differentials.Results
MUC18 siRNA reduced IL-13-mediated eotaxin-3 (183 ± 44 vs. 380 ± 59 pg/mL, p < 0.05), while MUC18 overexpression increased IL-13-mediated eotaxin-3 (95 ± 3 vs. 58 ± 3 pg/mL, p < 0.05) in HTBE cells. IL-13-treated Muc18 KO mice had a lower percentage of neutrophils in BAL than WT mice (25 ± 3 vs. 35 ± 3%, p = 0.0565).Conclusions
These results implicate MUC18 as a potential enhancer of airway inflammation in a type 2 cytokine (e.g., IL-13) milieu.15.
Objectives
To investigate the effect of chronic lung inflammation on the incidence and severity of collagen-induced arthritis in mice.Methods
Chronic lung inflammation in the form of silicosis was induced via intranasal application of silica particles. Immunization with collagen Type II commenced one week later and mice were sacrificed six weeks after booster immunization. Thereafter, silicosis was confirmed via flow cytometry and arthritis was evaluated performing knee and paw histology.Results
Pronounced lung inflammation in the silica-treated compared to PBS-treated control mice was demonstrated by significantly elevated broncho-alveolar lavage (BAL) cell count, attributable to increased numbers of macrophages and granulocytes. Inflammation in the lungs was not associated with elevated PAD2 and PAD4 expression, yet silica treated animals had significantly higher aCCP serum titers. However, lung inflammation did not lead to an increase in the incidence of arthritis, nor did it exacerbate the macroscopic or histologic joint scores.Conclusions
Chronic lung inflammation resulting from silicosis does not aggravate collagen-induced arthritis in mice.16.
Stephen P. J. Macdonald Erika Bosio Claire Neil Glenn Arendts Sally Burrows Lisa Smart Simon G. A. Brown Daniel M. Fatovich 《Inflammation research》2017,66(7):611-619
Objective and design
Resistin and neutrophil gelatinase-associated lipocalin (NGAL) are upregulated in circulating leucocytes in sepsis, but the significance of this is uncertain. We evaluated associations between Resistin and NGAL with endothelial cell activation and clinical outcomes in a prospective observational study in the Emergency Department (ED).Methods
Serum levels of Resistin, NGAL, inflammatory cytokines (IL-6, IL-10) and soluble endothelial adhesion molecules (VCAM-1, ICAM-1) were measured at defined time points up to 24 h. Patterns and relationships between markers were investigated using linear mixed regression models. Predictive values for clinical outcomes for markers at enrollment were assessed by logistic regression and receiver operator characteristic (ROC) curves.Results
186 participants (89 septic-shock, 69 sepsis, 28 uncomplicated infection) were compared with 29 healthy controls. Median Resistin and NGAL were higher in uncomplicated infection compared to controls, and in septic shock compared to non-shock sepsis. Resistin and NGAL correlated with IL-6 and IL-10, with VCAM-1 and ICAM-1, and with organ failure. Resistin and NGAL were associated with septic shock but had limited predictive utility for mortality.Conclusion
Resistin and NGAL correlate with expression of endothelial cell adhesion molecules in sepsis. Further evaluation of the role of Resistin and NGAL in sepsis pathogenesis is warranted.17.
Rachel Hamias Assaf Rudich George Greenberg Gabriel Szendro Talya Wolak 《Inflammation research》2018,67(3):265-275
Objective and design
Evaluating the pro-/anti-inflammatory activity of the C-terminal cleavage product of osteopontin in comparison to angiotensin 1–7.Material and subjects
Human coronary endothelial cells (hcEC) treated with conditioned media from human U937 macrophages.Treatment
Macrophages were (pre)treated with C-terminal, full-length or N-terminal osteopontin (OPN-C, OPN-FL, OPN-N, respectively), angiotensin II, angiotensin 1–7 or TNF-α. OPN-C modulatory capacity was compared to that of Ang1–7 in inhibiting subsequent Ag II, OPN-FL or OPN-N-induced macrophage-mediated endothelial inflammation.Methods
Protein expression of NFκB, IκB, vCAM-1 and iCAM-1 was assessed using western blot. Promotor activation by NFκB was also assessed by dual-luciferase reporter assay.Results
Conditioned media of macrophages treated with OPN-C induced hcECs’ NfκB activation to a lower degree than OPN-FL or OPN-N. Priming of macrophages with angiotensin 1–7 attenuated the endothelial pro-inflammatory effect induced by subsequent exposure of the macrophages to angiotensin II, OPN-FL or OPN-N. This was evidenced by both NfκB activation and vCAM and iCAM expression. In contrast, priming macrophages with OPN-C did not significantly attenuate the subsequent response to the pro-inflammatory cytokines.Conclusions
OPN-C induces lower macrophage-induced endothelial inflammation compared to OPN-FL or OPN-N, but unlike angiotensin 1–7, fails to prevent endothelial inflammation induced by subsequent pro-inflammatory macrophage stimulation.18.
Maísa Mota Antunes Alan Moreira Araújo Ariane Barros Diniz Rafaela Vaz Sousa Pereira Débora Moreira Alvarenga Bruna Araújo David Renata Monti Rocha Maria Alice Freitas Lopes Sarah Cozzer Marchesi Brenda Naemi Nakagaki Érika Carvalho Pedro Elias Marques Bernhard Ryffel Valérie Quesniaux Rodrigo Guabiraba Brito José Carlos Alves Filho Denise Carmona Cara Rafael Machado Rezende Gustavo Batista Menezes 《Inflammation research》2018,67(1):77-88
Objective and design
The aim of this study was to investigate the contribution of IL-33/ST2 axis in the onset and progression of acute liver injury using a mice model of drug-induced liver injury (DILI).Material and treatments
DILI was induced by overdose administration of acetaminophen (APAP) by oral gavage in wild-type BALB/c, ST2-deficient mice and in different bone marrow chimeras. Neutrophils were depleted by anti-Ly6G and macrophages with clodronate liposomes (CLL).Methods
Blood and liver were collected for biochemical, immunologic and genetic analyses. Mice were imaged by confocal intravital microscopy and liver non-parenchymal cells and hepatocytes were isolated for flow cytometry, genetic and immunofluorescence studies.Results
Acetaminophen overdose caused a massive necrosis and accumulation of immune cells within the liver, concomitantly with IL-33 and chemokine release. Liver non-parenchymal cells were the major sensors for IL-33, and amongst them, neutrophils were the major players in amplification of the inflammatory response triggered by IL-33/ST2 signalling pathway.Conclusion
Blockage of IL-33/ST2 axis reduces APAP-mediated organ injury by dampening liver chemokine release and activation of resident and infiltrating liver non-parenchymal cells.19.
Arunwan Udomkasemsab Chattraya Ngamlerst Poom Adisakwattana Amornrat Aroonnual Rungsunn Tungtrongchitr Pattaneeya Prangthip 《BMC complementary and alternative medicine》2018,18(1):344