scholarly journals Surfactant protein-D modulation of pulmonary macrophage phenotype is controlled by S-nitrosylation

2019 ◽  
Vol 317 (5) ◽  
pp. L539-L549 ◽  
Author(s):  
Chang-Jiang Guo ◽  
Elena N. Atochina-Vasserman ◽  
Elena Abramova ◽  
Ley Cody Smith ◽  
Michael F. Beers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Macrophage Phenotype ◽  
Oligomeric State ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Cellular Recruitment

Surfactant protein-D (SP-D) is a regulator of pulmonary innate immunity whose oligomeric state can be altered through S-nitrosylation to regulate its signaling function in macrophages. Here, we examined how nitrosylation of SP-D alters the phenotypic response of macrophages to stimuli both in vivo and in vitro. Bronchoalveolar lavage (BAL) from C57BL6/J and SP-D-overexpressing (SP-D OE) mice was incubated with RAW264.7 cells ± LPS. LPS induces the expression of the inflammatory genes Il1b and Nos2, which is reduced 10-fold by SP-D OE-BAL. S-nitrosylation of the SP-D OE-BAL (SNO-SP-D OE-BAL) abrogated this inhibition. SNO-SP-D OE-BAL alone induced Il1b and Nos2 expression. PCR array analysis of macrophages incubated with SP-D OE-BAL (±LPS) shows increased expression of repair genes, Ccl20, Cxcl1, and Vcam1, that was accentuated by LPS. LPS increases inflammatory gene expression, Il1a, Nos2, Tnf, and Ptgs2, which was accentuated by SNO-SP-D OE-BAL but inhibited by SP-D OE-BAL. The transcription factor NF-κB was identified as a target for SNO-SP-D by IPA, which was confirmed by Trans-AM ELISA in vitro. In vivo, SP-D overexpression increases the burden of infection in a Pneumocystis model while increasing cellular recruitment. Expression of iNOS and the production of NO metabolites were significantly reduced in SP-D OE mice relative to C57BL6/J. Inflammatory gene expression was increased in infected C57BL6/J mice but decreased in SP-D OE. SP-D oligomeric structure was disrupted in C57BL6/J infected mice but unaltered within SP-D OE. Thus SP-D modulates macrophage phenotype and the balance of multimeric to trimeric SP-D is critical to this regulation.

scholarly journals TMIC-27. GLIOMA CELLS INDUCE ‘EPIGENETIC MEMORY’ IN MICROGLIA AND BLOCK INFLAMMATORY GENE EXPRESSION- IN VITRO AND IN VIVO FINDINGS

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi262-vi262
Author(s):  
Bozena Kaminska ◽  
Marta Maleszewska ◽  
Aleksandra Steranka ◽  
Magdalena Smiech ◽  
Beata Kaza ◽  
...  
Keyword(s):  
Gene Expression ◽  
Glioma Cells ◽  
Epigenetic Memory ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene

Targeted adenovirus mediated inhibition of NF-κB-dependent inflammatory gene expression in endothelial cells in vitro and in vivo

2013 ◽  
Vol 166 (1) ◽  
pp. 57-65 ◽  
Author(s):  
J.M. Kułdo ◽  
S.A. Ásgeirsdóttir ◽  
P.J. Zwiers ◽  
A.R. Bellu ◽  
M.G. Rots ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene

scholarly journals Are Fried Foods Unhealthy? The Dietary Peroxidized Fatty Acid, 13-HPODE, Induces Intestinal Inflammation In Vitro and In Vivo

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 926 ◽  
Author(s):  
Esra’a Keewan ◽  
Chandrakala Aluganti Narasimhulu ◽  
Michael Rohr ◽  
Simran Hamid ◽  
Sampath Parthasarathy
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Intestinal Epithelium ◽  
Intestinal Inflammation ◽  
Inflammatory Disorder ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Gut Mucosa

Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder characterized by progressive inflammation and the erosion of the gut mucosa. Although the exact cause of IBD is unknown, multiple factors contribute to its complex pathogenesis. Diet is one such factor and a strong correlation exists between the western-style, high fat diets (HFDs) and IBD incidence rates. In this study, we propose that the peroxidized fatty acid components of HFDs could contribute to inflammation of the gut. The inflammatory nature of peroxidized linoleic acid (13-HPODE), was confirmed in vitro by analyzing pro-inflammatory gene expression in Caco-2 cells via RT-PCR and ELISA. Additionally, peroxide induced apoptosis was tested by Annexin-V fluorescent staining, while permeability was tested by FITC-dextran flux and TEER. The 13-HPODE-induced inflammation of intestinal epithelium was evaluated in vivo by analyzing pro-inflammatory cytokines under acute and chronic conditions after feeding 13-HPODE to C57BL/6J mice. Our data show that 13-HPODE significantly induced pro-inflammatory gene expression of TNF-α and MCP-1 in vitro, most notably in differentiated Caco-2 cells. Further, acute and chronic 13-HPODE treatments of mice similarly induced pro-inflammatory cytokine expression in the epithelium of both the proximal and distal small intestines, resident immune cells in Peyer’s patches and peritoneal macrophages. The results of this study not only confirm the pro-inflammatory properties of peroxidized fats on the gut mucosa, but for the first time demonstrate their ability to differentially induce pro-inflammatory gene expression and influence permeability in the intestinal epithelium and mucosal cells. Collectively, our results suggest that the immunogenic properties of HFD’s in the gut may be partly caused by peroxide derivatives, providing potential insight into how these diets contribute to exacerbations of IBD.

scholarly journals LIGHT controls distinct homeostatic and inflammatory gene expression profiles in esophageal fibroblasts via differential HVEM and LTβR-mediated mechanisms

2021 ◽  
Author(s):  
Mario C. Manresa ◽  
Amanda Wu ◽  
Quan M. Nhu ◽  
Austin W. T. Chiang ◽  
Kevin Okamoto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Gene Signature ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Primary Fibroblasts ◽  
Inflammatory Phenotype

AbstractFibroblasts mediate tissue remodeling in eosinophilic esophagitis (EoE), a chronic allergen-driven inflammatory pathology. Diverse fibroblast subtypes with homeostasis-regulating or inflammatory profiles have been recognized in various tissues, but which mediators induce these alternate differentiation states remain largely unknown. We recently identified that TNFSF14/LIGHT promotes an inflammatory esophageal fibroblast in vitro. Herein we used esophageal biopsies and primary fibroblasts to investigate the role of the LIGHT receptors, herpes virus entry mediator (HVEM) and lymphotoxin-beta receptor (LTβR), and their downstream activated pathways, in EoE. In addition to promoting inflammatory gene expression, LIGHT down-regulated homeostatic factors including WNTs, BMPs and type 3 semaphorins. In vivo, WNT2B+ fibroblasts were decreased while ICAM-1+ and IL-34+ fibroblasts were expanded in EoE, suggesting that a LIGHT-driven gene signature was imprinted in EoE versus normal esophageal fibroblasts. HVEM and LTβR overexpression and deficiency experiments demonstrated that HVEM regulates a limited subset of LIGHT targets, whereas LTβR controls all transcriptional effects. Pharmacologic blockade of the non-canonical NIK/p100/p52-mediated NF-κB pathway potently silenced LIGHT’s transcriptional effects, with a lesser role found for p65 canonical NF-κB. Collectively, our results show that LIGHT promotes differentiation of esophageal fibroblasts toward an inflammatory phenotype and represses homeostatic gene expression via a LTβR-NIK-p52 NF-κB dominant pathway.

scholarly journals Surfactant Protein D Increases Phagocytosis of Hypocapsular Cryptococcus neoformans by Murine Macrophages and Enhances Fungal Survival

2009 ◽  
Vol 77 (7) ◽  
pp. 2783-2794 ◽  
Author(s):  
Scarlett Geunes-Boyer ◽  
Timothy N. Oliver ◽  
Guilhem Janbon ◽  
Jennifer K. Lodge ◽  
Joseph Heitman ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Defense Mechanisms ◽  
Protein A ◽  
Surfactant Protein ◽  
Immune Defense ◽  
Surfactant Protein D ◽  
Wild Type ◽  
Phagocytic Cells

ABSTRACT Cryptococcus neoformans is a facultative intracellular opportunistic pathogen and the leading cause of fungal meningitis in humans. In the absence of a protective cellular immune response, the inhalation of C. neoformans cells or spores results in pulmonary infection. C. neoformans cells produce a polysaccharide capsule composed predominantly of glucuronoxylomannan, which constitutes approximately 90% of the capsular material. In the lungs, surfactant protein A (SP-A) and SP-D contribute to immune defense by facilitating the aggregation, uptake, and killing of many microorganisms by phagocytic cells. We hypothesized that SP-D plays a role in C. neoformans pathogenesis by binding to and enhancing the phagocytosis of the yeast. Here, the abilities of SP-D to bind to and facilitate the phagocytosis and survival of the wild-type encapsulated strain H99 and the cap59Δ mutant hypocapsular strain are assessed. SP-D binding to cap59Δ mutant cells was approximately sixfold greater than binding to wild-type cells. SP-D enhanced the phagocytosis of cap59Δ cells by approximately fourfold in vitro. To investigate SP-D binding in vivo, SP-D−/− mice were intranasally inoculated with Alexa Fluor 488-labeled cap59Δ or H99 cells. By confocal microscopy, a greater number of phagocytosed C. neoformans cells in wild-type mice than in SP-D−/− mice was observed, consistent with in vitro data. Interestingly, SP-D protected C. neoformans cells against macrophage-mediated defense mechanisms in vitro, as demonstrated by an analysis of fungal viability using a CFU assay. These findings provide evidence that C. neoformans subverts host defense mechanisms involving surfactant, establishing a novel virulence paradigm that may be targeted for therapy.

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