17 results on '"Dia Xenaki"'
Search Results
2. Dietary ω-6 polyunsaturated fatty acid arachidonic acid increases inflammation, but inhibits ECM protein expression in COPD
- Author
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Sandra Rutting, Michael Papanicolaou, Dia Xenaki, Lisa G. Wood, Alexander M. Mullin, Philip M. Hansbro, and Brian G. Oliver
- Subjects
COPD ,ω-6 PUFAs ,Airway inflammation ,Remodelling ,Human pulmonary fibroblasts ,Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Background The obesity paradox in COPD describes protective effects of obesity on lung pathology and inflammation. However, the underlying relationships between obesity, diet and disease outcomes in COPD are not fully understood. In this study we measured the response to dietary fatty acids upon markers of inflammation and remodelling in human lung cells from people with and without COPD. Methods Pulmonary fibroblasts were challenged with ω-3 polyunsaturated fatty acids (PUFAs), ω-6 PUFAs, saturated fatty acids (SFAs) or the obesity-associated cytokine TNFα. After 48–72 h release of the pro-inflammatory cytokines interleukin (IL)-6 and CXCL8 was measured using ELISA and mRNA expression and deposition of the extracellular matrix (ECM) proteins fibronectin, type I collagen, tenascin and perlecan were measured using qPCR or ECM ELISA, respectively. Results Challenge with the ω-6 PUFA arachidonic acid (AA), but not ω-3 PUFAs or SFAs, resulted in increased IL-6 and CXCL8 release from fibroblasts, however IL-6 and CXCL8 release was reduced in COPD (n = 19) compared to non-COPD (n = 36). AA-induced cytokine release was partially mediated by downstream mediators of cyclooxygenase (COX)-2 in both COPD and non-COPD. In comparison, TNFα-induced IL-6 and CXCL8 release was similar in COPD and non-COPD, indicating a specific interaction of AA in COPD. In patients with or without COPD, regression analysis revealed no relationship between BMI and cytokine release. In addition, AA, but not SFAs or ω-3 PUFAs reduced the basal deposition of fibronectin, type I collagen, tenascin and perlecan into the ECM in COPD fibroblasts. In non-COPD fibroblasts, AA-challenge decreased basal deposition of type I collagen and perlecan, but not fibronectin and tenascin. Conclusions This study shows that AA has disease-specific effects on inflammation and ECM protein deposition. The impaired response to AA in COPD might in part explain why obesity appears to have less detrimental effects in COPD, compared to other lung diseases.
- Published
- 2018
- Full Text
- View/download PDF
3. Heightened response to e-cigarettes in COPD
- Author
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Jack Bozier, Sandra Rutting, Dia Xenaki, Matthew Peters, Ian Adcock, and Brian G. Oliver
- Subjects
Medicine - Published
- 2019
- Full Text
- View/download PDF
4. Dietary Fatty Acids Amplify Inflammatory Responses to Infection through p38 MAPK Signaling
- Author
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Philip M. Hansbro, Jay C. Horvat, Lisa Wood, Jack Bozier, Razia Zakarya, Dia Xenaki, Sandra Rutting, and Brian G. Oliver
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,chemistry.chemical_classification ,medicine.medical_treatment ,Clinical Biochemistry ,Respiratory infection ,Cell Biology ,Pharmacology ,Proinflammatory cytokine ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,Cytokine ,Immune system ,030228 respiratory system ,chemistry ,medicine ,Arachidonic acid ,Lipoteichoic acid ,Interleukin 8 ,Molecular Biology ,Polyunsaturated fatty acid - Abstract
Obesity is an important risk factor for severe asthma exacerbations, which are mainly caused by respiratory infections. Dietary fatty acids, which are increased systemically in obese patients and are further increased after high-fat meals, affect the innate immune system and may contribute to dysfunctional immune responses to respiratory infection. In this study we investigated the effects of dietary fatty acids on immune responses to respiratory infection in pulmonary fibroblasts and a bronchial epithelial cell line (BEAS-2B). Cells were challenged with BSA-conjugated fatty acids (ω-6 polyunsaturated fatty acids [PUFAs], ω-3 PUFAs, or saturated fatty acids [SFAs]) +/- the viral mimic polyinosinic:polycytidylic acid (poly[I:C]) or bacterial compound lipoteichoic acid (LTA), and release of proinflammatory cytokines was measured. In both cell types, challenge with arachidonic acid (AA) (ω-6 PUFA) and poly(I:C) or LTA led to substantially greater IL-6 and CXCL8 release than either challenge alone, demonstrating synergy. In epithelial cells, palmitic acid (SFA) combined with poly(I:C) also led to greater IL-6 release. The underlying signaling pathways of AA and poly(I:C)- or LTA-induced cytokine release were examined using specific signaling inhibitors and IB. Cytokine production in pulmonary fibroblasts was prostaglandin dependent, and synergistic upregulation occurred via p38 mitogen-activated protein kinase signaling, whereas cytokine production in bronchial epithelial cell lines was mainly mediated through JNK and p38 mitogen-activated protein kinase signaling. We confirmed these findings using rhinovirus infection, demonstrating that AA enhances rhinovirus-induced cytokine release. This study suggests that during respiratory infection, increased levels of dietary ω-6 PUFAs and SFAs may lead to more severe airway inflammation and may contribute to and/or increase the severity of asthma exacerbations.
- Published
- 2019
5. Autophagy Activation in Asthma Airways Remodeling
- Author
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Kielan Darcy McAlinden, Dia Xenaki, Saeid Ghavami, Brian G. Oliver, Deepak A. Deshpande, Pawan K. Sharma, Mehra Haghi, and Sukhwinder Singh Sohal
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Clinical Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,Medicine ,Molecular Biology ,Lung function ,Asthma ,COPD ,business.industry ,Autophagy ,Disease progression ,Cell Biology ,respiratory system ,medicine.disease ,Epithelium ,respiratory tract diseases ,030104 developmental biology ,medicine.anatomical_structure ,030228 respiratory system ,Immunology ,Immunohistochemistry ,Airway ,business - Abstract
Current asthma therapies fail to target airway remodeling that correlates with asthma severity driving disease progression that ultimately leads to loss of lung function. Macroautophagy (hereinafte...
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- 2019
6. Airway smooth muscle cells from severe asthma patients with fixed airflow obstruction are responsive to steroid and bronchodilator treatment
- Author
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Brian G. Oliver, Karosham D. Reddy, Sandra Rutting, Melissa Baraket, Gregory G. King, Katrina O. Tonga, David G. Chapman, and Dia Xenaki
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Pulmonary and Respiratory Medicine ,medicine.drug_class ,Severe asthma ,medicine.medical_treatment ,Airflow obstruction ,Steroid ,03 medical and health sciences ,0302 clinical medicine ,Bronchodilator ,Medicine ,030212 general & internal medicine ,business.industry ,digestive, oral, and skin physiology ,Original Research Letters ,food and beverages ,Airway smooth muscle ,respiratory system ,In vitro ,respiratory tract diseases ,030228 respiratory system ,Immunology ,business ,Signalling pathways - Abstract
Asthma is characterised by recurrent symptoms associated with variable airflow obstruction and airway hyperresponsiveness, all of which are improved with combination inhaled corticosteroid (ICS)/long-acting β-agonist (LABA) treatment in mild-to-moderate asthma [1]. A proportion of patients however develop fixed airflow obstruction (FAO), despite optimised treatment. FAO is prevalent in up to 60% of patients with severe asthma and is associated with a more rapid decline in lung function and increased symptoms [2]. The underlying mechanisms of FAO in asthma are poorly understood; therefore, development of novel treatment strategies remains a challenge., Airway smooth muscle cells from severe asthma patients with FAO respond to β2-agonists and corticosteroids in vitro, and at a level similar to mild asthmatics. Intrinsic dysfunction of these signalling pathways is unlikely to contribute to FAO. https://bit.ly/3muvNsW
- Published
- 2021
7. Apoptosis signal-regulating kinase 1 inhibition attenuates human airway smooth muscle growth and migration in chronic obstructive pulmonary disease
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Kielan Darcy McAlinden, Anudeep Kota, Deepak A. Deshpande, Brian G. Oliver, Sukhwinder Singh Sohal, Mathew Suji Eapen, Pawan K. Sharma, Dia Xenaki, and Howard Vindin
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0301 basic medicine ,MAPK/ERK pathway ,biology ,MAP kinase kinase kinase ,business.industry ,Cell growth ,Kinase ,General Medicine ,respiratory system ,respiratory tract diseases ,03 medical and health sciences ,030104 developmental biology ,Mitogen-activated protein kinase ,Cancer research ,biology.protein ,Medicine ,ASK1 ,Protein kinase A ,business ,Platelet-derived growth factor receptor - Abstract
Increased airway smooth muscle (ASM) mass is observed in chronic obstructive pulmonary disease (COPD), which is correlated with disease severity and negatively affects lung function in these patients. Thus, there is clear unmet clinical need for finding new therapies which can target airway remodeling and disease progression in COPD. Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K) activated by various stress stimuli, including reactive oxygen species (ROS), tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS) and is known to regulate cell proliferation. ASM cells from COPD patients are hyperproliferative to mitogens in vitro. However, the role of ASK1 in ASM growth is not established. Here, we aim to determine the effects of ASK1 inhibition on ASM growth and pro-mitogenic signaling using ASM cells from COPD patients. We found greater expression of ASK1 in ASM bundles of COPD lung when compared with non-COPD. Pre-treatment of ASM cells with highly selective ASK1 inhibitor, TC ASK 10 resulted in a dose-dependent reduction in mitogen (FBS, PDGF, and EGF; 72 h)-induced ASM growth as measured by CyQUANT assay. Further, molecular targetting of ASK1 using siRNA in ASM cells prevented mitogen-induced cell growth. In addition, to anti-mitogenic potential, ASK1 inhibitor also prevented TGFβ1-induced migration of ASM cells in vitro. Immunoblotting revealed that anti-mitogenic effects are mediated by C-Jun N-terminal kinase (JNK) and p38MAP kinase-signaling pathways as evident by reduced phosphorylation of downstream effectors JNK1/2 and p38MAP kinases, respectively, with no effect on extracellular signal-regulated kinase (ERK) 1/2 (ERK1/2). Collectively, these findings establish the anti-mitogenic effect of ASK1 inhibition and identify a novel pathway that can be targetted to reduce or prevent excessive ASM mass in COPD.
- Published
- 2018
8. Short-chain fatty acids increase TNFα-induced inflammation in primary human lung mesenchymal cells through the activation of p38 MAPK
- Author
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Monique A. Malouf, Brian G. Oliver, Dia Xenaki, Lisa Wood, Philip M. Hansbro, Sandra Rutting, and Jay C. Horvat
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,Adult ,Male ,medicine.medical_specialty ,Physiology ,MAP Kinase Signaling System ,Myocytes, Smooth Muscle ,Inflammation ,Receptors, Cell Surface ,p38 Mitogen-Activated Protein Kinases ,Receptors, G-Protein-Coupled ,Butyric acid ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,medicine ,Free fatty acid receptor 3 ,Humans ,Interleukin 8 ,Lung ,Cells, Cultured ,Aged ,Chemistry ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Mesenchymal stem cell ,Interleukin-8 ,Mesenchymal Stem Cells ,Cell Biology ,Metabolism ,Fibroblasts ,Middle Aged ,Fatty Acids, Volatile ,030104 developmental biology ,Endocrinology ,030228 respiratory system ,Cell culture ,Tumor necrosis factor alpha ,Female ,medicine.symptom - Abstract
Short-chain fatty acids (SCFAs), produced as by-products of dietary fiber metabolism by gut bacteria, have anti-inflammatory properties and could potentially be used for the treatment of inflammatory diseases, including asthma. The direct effects of SCFAs on inflammatory responses in primary human lung mesenchymal cells have not been assessed. We investigated whether SCFAs can protect against tumor necrosis factor (TNF)α-induced inflammation in primary human lung fibroblasts (HLFs) and airway smooth muscle (ASM) cells in vitro. HLFs and ASM cells were exposed to SCFAs, acetate (C2:0), propionate (C3:0), and butyrate (C4:0) (0.01–25 mM) with or without TNFα, and the release of proinflammatory cytokines, IL-6, and CXCL8 was measured using ELISA. We found that none of the SCFAs suppressed TNFα-induced cytokine release. On the contrary, challenge with supraphysiological concentrations (10–25 mM), as might be used therapeutically, of propionate or butyrate in combination with TNFα resulted in substantially greater IL-6 and CXCL8 release from HLFs and ASM cells than challenge with TNFα alone, demonstrating synergistic effects. In ASM cells, challenge with acetate also enhanced TNFα-induced IL-6, but not CXCL8 release. Synergistic upregulation of IL-6 and CXCL8 was mediated through the activation of free fatty acid receptor (FFAR)3, but not FFAR2. The signaling pathways involved were further examined using specific inhibitors and immunoblotting, and responses were found to be mediated through p38 MAPK signaling. This study demonstrates that proinflammatory, rather than anti-inflammatory effects of SCFAs are evident in lung mesenchymal cells.
- Published
- 2018
9. Dietary ω-6 polyunsaturated fatty acid arachidonic acid increases inflammation, but inhibits ECM protein expression in COPD
- Author
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Dia Xenaki, Brian G. Oliver, Sandra Rutting, Michael Papanicolaou, Philip M. Hansbro, Lisa Wood, and Alexander M. Mullin
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,medicine.medical_treatment ,Respiratory System ,Gene Expression ,Tenascin ,Perlecan ,Extracellular matrix ,Pulmonary Disease, Chronic Obstructive ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Fatty Acids, Omega-6 ,Internal medicine ,ω-6 PUFAs ,medicine ,COPD ,Humans ,Cells, Cultured ,Aged ,lcsh:RC705-779 ,Inflammation ,chemistry.chemical_classification ,Extracellular Matrix Proteins ,Arachidonic Acid ,biology ,Research ,Remodelling ,lcsh:Diseases of the respiratory system ,Human pulmonary fibroblasts ,Fibroblasts ,Middle Aged ,respiratory tract diseases ,3. Good health ,Fibronectin ,030104 developmental biology ,Cytokine ,Endocrinology ,030228 respiratory system ,chemistry ,biology.protein ,Female ,Arachidonic acid ,Inflammation Mediators ,Type I collagen ,Airway inflammation ,Polyunsaturated fatty acid - Abstract
Background The obesity paradox in COPD describes protective effects of obesity on lung pathology and inflammation. However, the underlying relationships between obesity, diet and disease outcomes in COPD are not fully understood. In this study we measured the response to dietary fatty acids upon markers of inflammation and remodelling in human lung cells from people with and without COPD. Methods Pulmonary fibroblasts were challenged with ω-3 polyunsaturated fatty acids (PUFAs), ω-6 PUFAs, saturated fatty acids (SFAs) or the obesity-associated cytokine TNFα. After 48–72 h release of the pro-inflammatory cytokines interleukin (IL)-6 and CXCL8 was measured using ELISA and mRNA expression and deposition of the extracellular matrix (ECM) proteins fibronectin, type I collagen, tenascin and perlecan were measured using qPCR or ECM ELISA, respectively. Results Challenge with the ω-6 PUFA arachidonic acid (AA), but not ω-3 PUFAs or SFAs, resulted in increased IL-6 and CXCL8 release from fibroblasts, however IL-6 and CXCL8 release was reduced in COPD (n = 19) compared to non-COPD (n = 36). AA-induced cytokine release was partially mediated by downstream mediators of cyclooxygenase (COX)-2 in both COPD and non-COPD. In comparison, TNFα-induced IL-6 and CXCL8 release was similar in COPD and non-COPD, indicating a specific interaction of AA in COPD. In patients with or without COPD, regression analysis revealed no relationship between BMI and cytokine release. In addition, AA, but not SFAs or ω-3 PUFAs reduced the basal deposition of fibronectin, type I collagen, tenascin and perlecan into the ECM in COPD fibroblasts. In non-COPD fibroblasts, AA-challenge decreased basal deposition of type I collagen and perlecan, but not fibronectin and tenascin. Conclusions This study shows that AA has disease-specific effects on inflammation and ECM protein deposition. The impaired response to AA in COPD might in part explain why obesity appears to have less detrimental effects in COPD, compared to other lung diseases. Electronic supplementary material The online version of this article (10.1186/s12931-018-0919-4) contains supplementary material, which is available to authorized users.
- Published
- 2018
10. Dietary omega-6, but not omega-3, polyunsaturated or saturated fatty acids increase inflammation in primary lung mesenchymal cells
- Author
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Lisa Wood, Sandra Rutting, Brian G. Oliver, Philip M. Hansbro, Dia Xenaki, Jay C. Horvat, and Edmund M.T. Lau
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Male ,medicine.medical_specialty ,Physiology ,MAP Kinase Signaling System ,medicine.medical_treatment ,Inflammation ,Proinflammatory cytokine ,03 medical and health sciences ,chemistry.chemical_compound ,Phosphatidylinositol 3-Kinases ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,Fatty Acids, Omega-6 ,Fatty Acids, Omega-3 ,medicine ,Humans ,Interleukin 8 ,Interleukin 6 ,Extracellular Signal-Regulated MAP Kinases ,Lung ,Aged ,chemistry.chemical_classification ,Innate immune system ,biology ,Interleukin-6 ,Interleukin-8 ,NF-kappa B ,Mesenchymal Stem Cells ,Cell Biology ,Middle Aged ,030104 developmental biology ,Endocrinology ,Cytokine ,030228 respiratory system ,chemistry ,biology.protein ,Arachidonic acid ,Female ,medicine.symptom ,Polyunsaturated fatty acid - Abstract
Obesity is an important risk factor for developing severe asthma. Dietary fatty acids, which are increased in sera of obese individuals and after high-fat meals, activate the innate immune system and induce inflammation. This study investigated whether dietary fatty acids directly cause inflammation and/or synergize with obesity-induced cytokines in primary human pulmonary fibroblasts in vitro. Fibroblasts were challenged with BSA-conjugated fatty acids [ω-6 polyunsaturated fatty acids (PUFAs) and ω-3 PUFAs or saturated fatty acids (SFAs)], with or without TNF-α, and release of the proinflammatory cytokines, IL-6 and CXCL8, was measured. We found that the ω-6 PUFA arachidonic acid (AA), but not ω-3 PUFAs or SFAs, upregulates IL-6 and CXCL8 release. Combined AA and TNF-α challenge resulted in substantially greater cytokine release than either alone, demonstrating synergy. Synergistic upregulation of IL-6, but not CXCL8, was mainly mediated via cyclooxygenase (COX). Inhibition of p38 MAPK reduced CXCL8 release, induced by AA and TNF-α alone, but not in combination. Synergistic CXCL8 release, following AA and TNF-α challenge, was not medicated via a single signaling pathway (MEK1, JNK, phosphoinositide 3-kinase, and NF-κB) nor by hyperactivation of NF-κB or p38. To investigate if these findings occur in other airway cells, effects of AA in primary human airway smooth muscle (ASM) cells and human bronchial epithelial cells were also investigated. We found proinflammatory effects in ASM cells but not epithelial cells. This study suggests that diets rich in ω-6 PUFAs might promote airway inflammation via multiple pathways, including COX-dependent and -independent pathways, and in an obese person, may lead to more severe airway inflammation.
- Published
- 2018
11. F3/contactin and TAG1 play antagonistic roles in the regulation of sonic hedgehog-induced cerebellar granule neuron progenitor proliferation
- Author
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Andrew J.W. Furley, Takeshi Sakurai, Dia Xenaki, Martin Grumet, Kyoji Ohyama, Gianfranco Gennarini, Indira B. Martin, and Lynn Yoshida
- Subjects
Contactin 1 ,animal structures ,Cellular differentiation ,Morphogenesis ,Biology ,Mice ,Paracrine signalling ,Cerebellum ,Contactin 2 ,Animals ,Hedgehog Proteins ,Progenitor cell ,Sonic hedgehog ,Molecular Biology ,Cells, Cultured ,Cell Proliferation ,Neurons ,Cell adhesion molecule ,Cell Differentiation ,Anatomy ,Mice, Mutant Strains ,Cell biology ,embryonic structures ,biology.protein ,Signal transduction ,Signal Transduction ,Research Article ,Developmental Biology - Abstract
Modulation of the sonic hedgehog (SHH) pathway is a crucial factor in cerebellar morphogenesis. Stimulation of granule neuron progenitor (GNP) proliferation is a central function of SHH signalling, but how this is controlled locally is not understood. We show that two sequentially expressed members of the contactin (CNTN) family of adhesion molecules, TAG1 and F3, act antagonistically to control SHH-induced proliferation: F3 suppresses SHH-induced GNP proliferation and induces differentiation, whereas TAG1 antagonises F3. Production of GNPs in TAG1-null mice is delayed and reduced. F3 and TAG1 colocalise on GNPs with the related L1-like adhesion molecule NrCAM, and F3 fails to suppress the SHH-induced proliferation of NrCAM-deficient GNPs. We show that F3 and SHH both primarily affect a group of intermediate GNPs (IPs), which, though actively dividing, also express molecules associated with differentiation, including β-tubulin III (TuJ1) and TAG1. In vivo, intermediate progenitors form a discrete layer in the middle of the external germinal layer (mEGL), while F3 becomes expressed on the axons of postmitotic granule neurons as they leave the inner EGL (iEGL). We propose, therefore, that F3 acts as a localised signal in the iEGL that induces SHH-stimulated cells in the overlying mEGL to exit cell cycle and differentiate. By contrast, expression of TAG1 on GNPs antagonises this signal in the mEGL, preventing premature differentiation and sustaining GNP expansion in a paracrine fashion. Together, these findings indicate that CNTN and L1-like proteins play a significant role in modulating SHH-induced neuronal precursor proliferation.
- Published
- 2011
12. Short-chain fatty acids increase TNFα-induced inflammation in primary human lung mesenchymal cells through the activation of p38 MAPK.
- Author
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Rutting, Sandra, Dia Xenaki, Malouf, Monique, Horvat, Jay C., Wood, Lisa G., Hansbro, Philip M., and Oliver, Brian G.
- Subjects
- *
MITOGEN-activated protein kinases , *TUMOR necrosis factors , *MESENCHYMAL stem cells - Abstract
Short-chain fatty acids (SCFAs), produced as by-products of dietary fiber metabolism by gut bacteria, have antiinflammatory properties and could potentially be used for the treatment of inflammatory diseases, including asthma. The direct effects of SCFAs on inflammatory responses in primary human lung mesenchymal cells have not been assessed. We investigated whether SCFAs can protect against tumor necrosis factor (TNF)α-induced inflammation in primary human lung fibroblasts (HLFs) and airway smooth muscle (ASM) cells in vitro. HLFs and ASM cells were exposed to SCFAs, acetate (C2:0), propionate (C3:0), and butyrate (C4:0) (0.01-25 mM) with or without TNFα, and the release of proinflammatory cytokines, IL-6, and CXCL8 was measured using ELISA. We found that none of the SCFAs suppressed TNFα-induced cytokine release. On the contrary, challenge with supraphysiological concentrations (10-25 mM), as might be used therapeutically, of propionate or butyrate in combination with TNFα resulted in substantially greater IL-6 and CXCL8 release from HLFs and ASM cells than challenge with TNFα alone, demonstrating synergistic effects. In ASM cells, challenge with acetate also enhanced TNFα-induced IL-6, but not CXCL8 release. Synergistic upregulation of IL-6 and CXCL8 was mediated through the activation of free fatty acid receptor (FFAR)3, but not FFAR2. The signaling pathways involved were further examined using specific inhibitors and immunoblotting, and responses were found to be mediated through p38 MAPK signaling. This study demonstrates that proinflammatory, rather than anti-inflammatory effects of SCFAs are evident in lung mesenchymal cells. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
13. F3/Contactin acts as a modulator of neurogenesis during cerebral cortex development
- Author
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Dia Xenaki, Angela Polizzi, Antonella Bizzoca, Andrew J.W. Furley, Marco F. Pinto, Patrizia Corsi, and Gianfranco Gennarini
- Subjects
Axonal glycoproteins ,Neurogenesis ,Notch signaling pathway ,Biology ,Animals, Genetically Modified ,Mice ,Downregulation and upregulation ,Contactin 1 ,medicine ,Animals ,Humans ,Molecular Biology ,Notch signaling ,Regulation of gene expression ,Cerebral Cortex ,Neurons ,Receptors, Notch ,Cortical precursor proliferation/differentiation ,Wild type ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Cell Biology ,Anatomy ,Transgenic misexpression ,Cell biology ,Cortex (botany) ,Gene regulation ,Corticogenesis ,medicine.anatomical_structure ,Cerebral cortex ,Developmental Biology ,Signal Transduction - Abstract
The expression of the cell recognition molecule F3/Contactin (CNTN1) is generally associated with the functions of post-mitotic neurons. In the embryonic cortex, however, we find it expressed by proliferating ventricular zone (VZ) precursors. In contrast to previous findings in the developing cerebellum, F3/Contactin transgenic overexpression in the early cortical VZ promotes proliferation and expands the precursor pool at the expense of neurogenesis. At later stages, when F3/Contactin levels subside, however, neurogenesis resumes, suggesting that F3/Contactin expression in the VZ is inversely related to neurogenesis and plays a role in a feedback control mechanism, regulating the orderly progression of cortical development. The modified F3/Contactin profile therefore results in delayed corticogenesis, as judged by downregulation in upper and lower layer marker expression and by BrdU birth dating, indicating that, in this transgenic model, increased F3/Contactin levels counteract neuronal precursor commitment. These effects also occur in primary cultures and are reproduced by addition of an F3/Fc fusion protein to wild type cultures. Together, these data indicate a completely novel function for F3/Contactin. Parallel changes in the generation of the Notch Intracellular Domain and in the expression of the Hes-1 transcription factor indicate that activation of the Notch pathway plays a role in this phenotype, consistent with previous in vitro reports that F3/Contactin is a Notch1 ligand.
- Published
- 2011
14. Additional file 1: of Dietary Ď -6 polyunsaturated fatty acid arachidonic acid increases inflammation, but inhibits ECM protein expression in COPD
- Author
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Rutting, Sandra, Papanicolaou, Michael, Dia Xenaki, Wood, Lisa, Mullin, Alexander, Hansbro, Philip, and Oliver, Brian
- Subjects
respiratory system ,respiratory tract diseases ,3. Good health - Abstract
Figure S1. Similar response to arachidonic acid in patients with non-smoking related end-stage lung disease and patients who underwent lung resection for thoracic malignancies. (DOC 153 kb)
15. Additional file 1: of Dietary Ď -6 polyunsaturated fatty acid arachidonic acid increases inflammation, but inhibits ECM protein expression in COPD
- Author
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Rutting, Sandra, Papanicolaou, Michael, Dia Xenaki, Wood, Lisa, Mullin, Alexander, Hansbro, Philip, and Oliver, Brian
- Subjects
respiratory system ,respiratory tract diseases ,3. Good health - Abstract
Figure S1. Similar response to arachidonic acid in patients with non-smoking related end-stage lung disease and patients who underwent lung resection for thoracic malignancies. (DOC 153 kb)
16. NrCAM modulates sonic hedgehog signalling by controlling smoothened translocation in the cilium
- Author
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O Weeranantanapan, Andrew J.W. Furley, Dia Xenaki, and B Basu
- Subjects
Genetics ,biology ,Cilium ,Mutant ,Wild type ,Cell Biology ,Molecular medicine ,Cell biology ,embryonic structures ,Poster Presentation ,biology.protein ,Sonic hedgehog ,Receptor ,Smoothened ,Developmental biology - Abstract
Objective: Cerebellar development involves a spurt of proliferation in external granule layer (EGL) in response to shh, causing granule neuron precursors (GNPs) to proliferate. These cells subsequently differentiate into granule neurons in the inner granule layer (IGL). F3, a CNTN family molecule, can interact with NrCAM to switch GNPs from proliferation to differentiation. We aim to identify the role of NrCAM in the sonic hedgehog response in GNPs. Methods: GNPs were extracted from wildtype and NrCAM mutant P5 cerebella using Percoll gradient centrifugation. Proliferation response to shh was measured using EdU in presence/absence of F3-Fc. GNPs treated with shh/SAG were stained with antibodies against Arl13b and smo to look for differences in cilia size and smo occupancy after different treatment times. Results: NrCAM-/- and wildtype GNPs both proliferated equally in response to shh. F3 was found to block the proliferation response in wildtype but not in NrCAM-/- GNPs. F3 also failed to affect proliferation in SmoA1 GNPs with a constitutively active smo suggesting that the F3-NrCAM mediated block lay upstream of Smo. NrCAM was detected in wildtype cilia and Smo localization was affected in NrCAM-/- GNPs. No differences in cilia length were observed. Conclusion: Our results suggest that NrCAM affects shh-mediated proliferation by controlling smo movement into the cilium.
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17. F3/contactin and TAG1 play antagonistic roles in the regulation of sonic hedgehog-induced cerebellar granule neuron progenitor proliferation.
- Author
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Dia Xenaki, Martin, Indira B., Yoshida, Lynn, Ohyama, Kyoji, Gennarini, Gianfranco, Grumet, Martin, Sakurai, Takeshi, and Furley, Andrew J. W.
- Subjects
- *
NEURONS - Abstract
An abstract of the article "F3/Contactin and TAG1 Play Antagonistic Roles in the Regulation of Sonic Hedgehog-Induced Cerebellar Granule Neuron Progenitor Proliferation," by Dia Xenaki and colleagues is presented.
- Published
- 2011
- Full Text
- View/download PDF
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