scholarly journals Classical swine fever virus inhibits nitric oxide production in infected macrophages

2007 ◽  
Vol 88 (11) ◽  
pp. 3007-3012 ◽  
Author(s):  
K. M. Zaffuto ◽  
M. E. Piccone ◽  
T. G. Burrage ◽  
C. A. Balinsky ◽  
G. R. Risatti ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Classical Swine Fever Virus ◽  
Interleukin 1 ◽  
Classical Swine Fever ◽  
Fever Virus ◽  
Nitric Oxide Production ◽  
Mrna Levels ◽  
Transcriptional Responses ◽  
Oxide Production ◽  
Arginase 1

Classical swine fever virus (CSFV)–macrophage interactions during infection were analysed by examining macrophage transcriptional responses via microarray. Eleven genes had increased mRNA levels (>2.5-fold, P<0.05) in infected cell cultures, including arginase-1, an inhibitor of nitric oxide production, phosphoinositide 3-kinase, chemokine receptor 4 and interleukin-1β. Lower levels of nitric oxide and increased arginase activity were found in CSFV-infected macrophages. These changes in gene expression in macrophages suggest viral modulation of host expression to suppress nitric oxide production.

scholarly journals The 12-HHT/BLT2/NO Axis Is Associated to the Wound Healing and Skin Condition in Different Glycaemic States

2019 ◽  
Vol 7 (4) ◽  
pp. 65
Author(s):  
Leguina-Ruzzi ◽  
Ortiz Diban ◽  
Velarde
Keyword(s):  
Nitric Oxide ◽  
Wound Healing ◽  
Tight Junction ◽  
Skin Condition ◽  
Inos Mrna ◽  
Nitric Oxide Production ◽  
Mrna Levels ◽  
Oxide Production

Type 2 diabetes affects over 340 million people worldwide. This condition can go unnoticed and undiagnosed for years, leading to a late stage where high glycaemia produces complications such as delayed wound healing. Studies have shown that 12-HHT through BLT2, accelerates keratinocyte migration and wound healing. Additionally, evidence has shown the role of nitric oxide as a pro-regenerative mediator, which is decreased in diabetes. Our main goal was to study the association between the 12-HHT/BLT2 axis and the nitric oxide production in wound healing under different glycaemia conditions. For that purpose, we used in vivo and in vitro models. Our results show that the skin from diabetic mice showed reduced BLT2 and iNOS mRNA, TEER, 12-HHT, nitrites, and tight junction levels, accompanied by higher MMP9 mRNA levels. Furthermore, a positive correlation between BLT2 mRNA and nitrites was observed. In vitro, HaCaT-BLT2 cells showed higher nitric oxide and tight junction levels, and reduced MMP9 mRNA levels, compared to mock-keratinocytes under low and high glucose condition. The wound healing capacity was associated with higher nitric oxide production and was affected by the NOS inhibition. We suggest that the BLT2 expression improves the keratinocyte response to hyperglycaemia, associated with the production of nitric oxide.

Nicotinamide Prevents Interleukin-1 Effects on Accumulated Insulin Release and Nitric Oxide Production in Rat Islets of Langerhans

Diabetes ◽  
1994 ◽  
Vol 43 (6) ◽  
pp. 770-777 ◽  
Author(s):  
H. U. Andersen ◽  
K. H. Jorgensen ◽  
J. Egeberg ◽  
T. Mandrup-Poulsen ◽  
J. Nerup
Keyword(s):  
Nitric Oxide ◽  
Insulin Release ◽  
Islets Of Langerhans ◽  
Interleukin 1 ◽  
Nitric Oxide Production ◽  
Rat Islets ◽  
Oxide Production ◽  
Rat Islets Of Langerhans

scholarly journals Candida albicans Chitin Increases Arginase-1 Activity in Human Macrophages, with an Impact on Macrophage Antimicrobial Functions

mBio ◽  
2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Jeanette Wagener ◽  
Donna M. MacCallum ◽  
Gordon D. Brown ◽  
Neil A. R. Gow
Keyword(s):  
Nitric Oxide ◽  
Candida Albicans ◽  
Fungal Pathogen ◽  
Arginase Activity ◽  
Nitric Oxide Production ◽  
Fungal Cell ◽  
Oxide Production ◽  
Arginase 1 ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

ABSTRACT   The opportunistic human fungal pathogen Candida albicans can cause a variety of diseases, ranging from superficial mucosal infections to life-threatening systemic infections. Phagocytic cells of the innate immune response, such as neutrophils and macrophages, are important first-line responders to an infection and generate reactive oxygen and nitrogen species as part of their protective antimicrobial response. During an infection, host cells generate nitric oxide through the enzyme inducible nitric oxide synthase (iNOS) to kill the invading pathogen. Inside the phagocyte, iNOS competes with the enzyme arginase-1 for a common substrate, the amino acid l -arginine. Several pathogenic species, including bacteria and parasitic protozoans, actively modulate the production of nitric oxide by inducing their own arginases or the host’s arginase activity to prevent the conversion of l -arginine to nitric oxide. We report here that C. albicans blocks nitric oxide production in human-monocyte-derived macrophages by induction of host arginase activity. We further determined that purified chitin (a fungal cell wall polysaccharide) and increased chitin exposure at the fungal cell wall surface induces this host arginase activity. Blocking the C. albicans -induced arginase activity with the arginase-specific substrate inhibitor N ω-hydroxy-nor-arginine (nor-NOHA) or the chitinase inhibitor bisdionin F restored nitric oxide production and increased the efficiency of fungal killing. Moreover, we determined that C. albicans influences macrophage polarization from a classically activated phenotype toward an alternatively activated phenotype, thereby reducing antimicrobial functions and mediating fungal survival. Therefore, C. albicans modulates l -arginine metabolism in macrophages during an infection, potentiating its own survival. IMPORTANCE The availability and metabolism of amino acids are increasingly recognized as crucial regulators of immune functions. In acute infections, the conversion of the “conditionally essential” amino acid l -arginine by the inducible nitric oxide synthase to nitric oxide is a resistance factor that is produced by the host to fight pathogens. Manipulation of these host defense mechanisms by the pathogen can be key to successful host invasion. We show here that the human opportunistic fungal pathogen Candida albicans influences l -arginine availability for nitric oxide production by induction of the substrate-competing host enzyme arginase-1. This led to a reduced production of nitric oxide and, moreover, reduced eradication of the fungus by human macrophages. We demonstrate that blocking of host arginase-1 activity restored nitric oxide production and increased the killing potential of macrophages. These results highlight the therapeutic potential of l -arginine metabolism in fungal diseases.

scholarly journals Mutations in Classical Swine Fever Virus NS4B Affect Virulence in Swine

2009 ◽  
Vol 84 (3) ◽  
pp. 1536-1549 ◽  
Author(s):  
I. Fernandez-Sainz ◽  
D. P. Gladue ◽  
L. G. Holinka ◽  
V. O'Donnell ◽  
I. Gudmundsdottir ◽  
...  
Keyword(s):  
Classical Swine Fever Virus ◽  
Transcriptional Activation ◽  
Interleukin 1 ◽  
Classical Swine Fever ◽  
Fever Virus ◽  
Protein Domain ◽  
Predicted Amino Acid Sequence ◽  
Nonstructural Proteins ◽  
Peripheral Blood Mononuclear ◽  
Mrna Transfection

ABSTRACT NS4B is one of the nonstructural proteins of classical swine fever virus (CSFV), the etiological agent of a severe, highly lethal disease of swine. Protein domain analysis of the predicted amino acid sequence of the NS4B protein of highly pathogenic CSFV strain Brescia (BICv) identified a putative Toll/interleukin-1 receptor (TIR)-like domain. This TIR-like motif harbors two conserved domains, box 1 and box 2, also observed in other members of the TIR superfamily, including Toll-like receptors (TLRs). Mutations within the BICv NS4B box 2 domain (V2566A, G2567A, I2568A) produced recombinant virus NS4B.VGIv, with an altered phenotype displaying enhanced transcriptional activation of TLR-7-induced genes in swine macrophages, including a significant sustained accumulation of interleukin-6 (IL-6) mRNA. Transfection of swine macrophages with the wild-type NS4B gene partially blocked the TLR-7-activating effect of imiquimod (R837), while transfection with the NS4B gene harboring mutations in either of the putative boxes displayed decreased blocking activity. NS4B.VGIv showed an attenuated phenotype in swine, displaying reduced replication in the oronasal cavity and limited spread from the inoculation site to secondary target organs. Furthermore, the level and duration of IL-6 production in the tonsils of pigs intranasally inoculated with NS4B.VGIv were significantly higher than those for animals infected with BICv. The peak of IL-6 production in infected animals paralleled the ability of animals infected with NS4B.VGIv to resist challenge with virulent BICv. Interestingly, treatment of peripheral blood mononuclear cell cultures with recombinant porcine IL-6 results in a significant decrease in BICv replication.

scholarly journals BDKRB2 +9/−9 bp polymorphisms influence BDKRB2 expression levels and NO production in knee osteoarthritis

2016 ◽  
Vol 242 (4) ◽  
pp. 422-428 ◽  
Author(s):  
Shuo Chen ◽  
Lei Zhang ◽  
Ruonan Xu ◽  
Yunfan Ti ◽  
Yunlong Zhao ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Knee Osteoarthritis ◽  
Synovial Tissue ◽  
No Production ◽  
Lower Grade ◽  
Nitric Oxide Production ◽  
Mrna Levels ◽  
Expression Levels ◽  
Oxide Production ◽  
Synovial Tissues

The bradykinin B2 receptor (BDKRB2) plays a key role in the inflammation process of osteoarthritis. Nitric oxide has also long been considered to be a catabolic factor that contributes to inflammatory response and the osteoarthritis disease pathology. Several studies have reported that the BDKRB2 +9/−9 bp polymorphisms are associated with transcription of the receptor. However, the roles of BDKRB2 polymorphisms in inflammation in osteoarthritis remain unclear. This study enrolled 156 subjects with primary knee osteoarthritis and 58 healthy volunteers. BDKRB2 polymorphisms were genotyped, and the mRNA and protein levels of BDKRB2 in synovial tissues from osteoarthritis patients were measured by quantitative real-time polymerase chain reaction and western blot analysis, respectively. Nitric oxide production in serum from patients with osteoarthritis was measured using a nitric oxide assay kit. We found that the mean BDKRB2 mRNA levels were significantly higher in Kallgren-Lawrence grade-4 osteoarthritis patients than patients with lower grade osteoarthritis. The +9/−9 bp polymorphisms significantly affected the BDKRB2 mRNA and protein expression levels in synovial tissues from osteoarthritis subjects. Osteoarthritis patients with +9/−9 and −9/−9 genotypes had higher BDKRB2 expression levels in synovial tissue and nitric oxide production in serum. Moreover, positive correlation was found between the BDKRB2 levels in synovial tissue and nitric oxide production. Compared with health controls, significant increases of nitric oxide production in osteoarthritis were detected which were associated with increasing severity of osteoarthritis. Multiple linear regression analysis (adjusted for gender and age) showed serum nitric oxide level was positively associated with BDKRB2 polymorphism and Kallgren-Lawrence grade and was inversely associated with obesity. Our findings showed that the BDKRB2 +9/−9 bp polymorphisms affected the gene expression and nitric oxide production, which were associated with radiographic severity of osteoarthritis, suggesting that the BDKRB2 +9/ −9 bp polymorphisms may act as a genetic modulator of osteoarthritis, and play an essential role in inflammatory process in osteoarthritis.

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