Pharmacological inhibition of DDAH1 improves survival, haemodynamics and organ function in experimental septic shock

2014 ◽  
Vol 460 (2) ◽  
pp. 309-316 ◽  
Author(s):  
Zhen Wang ◽  
Simon Lambden ◽  
Valerie Taylor ◽  
Elizabeth Sujkovic ◽  
Manasi Nandi ◽  
...  
Keyword(s):  
Septic Shock ◽  
Cell Function ◽  
Immune Cell ◽  
Cardiovascular Function ◽  
Rodent Model ◽  
Morbidity And Mortality ◽  
Immune Cell Function ◽  
Organ Function ◽  
Experimental Septic Shock ◽  
First Time

The present study shows for the first time in the most relevant possible rodent model of shock that the DDAH1 inhibitor L-257 improves morbidity and mortality in septic shock by improving cardiovascular function without impairing the immune cell function.

scholarly journals OP0013 SEX DIFFERENCES IN AUTOIMMUNE DISEASE SUSCEPTIBILITY; A MULTI-OMIC APPROACH

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 8.1-8
Author(s):  
G. Robinson ◽  
K. Waddington ◽  
J. Peng ◽  
A. Radziszewska ◽  
H. Peckham ◽  
...  
Keyword(s):  
Sex Differences ◽  
Lipid Metabolism ◽  
Sex Hormones ◽  
Cell Function ◽  
Immune Cell ◽  
Density Lipoprotein ◽  
Hormone Treatment ◽  
Immune Cell Function ◽  
Immune Cell Subsets ◽  
Males And Females

Background:Males and females have altered immune responses resulting in variation in autoimmune and cardiovascular disease risk (CVR). Recently, these differences have played a role in the inflammatory response to COVID-19. Sex differences exist in the frequency and activity of immune-cell subsets but mechanisms underlying sexual dimorphism remain unknown. Juvenile-onset systemic lupus erythematosus (JSLE) is an autoimmune disorder that commonly emerges during puberty, has a strong female prevalence (female:male ratio, 4.5:1) and results in an increased CVR. JSLE is characterised by chronic inflammation and dyslipidaemia, where cardiovascular disease is a leading cause of mortality for patients. Our previous work identified a link between immune cell function and lipid metabolism in adult-onset SLE. We hypothesised that sex hormones could influence both lipid metabolism and immune cell function and this could determine sex-specific susceptibility to JSLE and associated CVR.Objectives:We investigated the role of sex hormones in modifying systemic lipid metabolism and inflammation.Methods:Nuclear magnetic resonance spectroscopy based serum metabolomics measuring over 130 lipoproteins (14-subsets with lipid compositions), flow cytometry measuring immune-cells, and RNA-sequencing were used to assess the metabolic and immune profile in young, pre/post-pubertal males (n=10/17) and females (n=10/23) and in individuals with gender-dysphoria (GD) under cross-hormone treatment (trans-male/female, n=26/25). This analysis was also performed on a cohort of post-pubertal male (n=12) and female (n=23) JSLE patients. Data was analysed by logistic regression, balanced random forest machine learning (BRF-ML), differential gene expression (DEG) and pathway analysis.Results:Post-pubertal males had significantly reduced cardio-protective high-density lipoprotein (HDL) subsets (p<0.0001) and increased cardio-pathogenic very-low-density lipoprotein subsets (p<0.0001) compared to females. These differences were not observed pre-puberty and were reversed significantly by cross-hormone treatment in GD individuals, suggesting that sex hormones regulate lipid metabolism in-vivo.BRF-ML (28 immune-cell subsets) identified an increased frequency of anti-inflammatory regulatory T-cells (Tregs) in post-pubertal males compared to females (p=0.0097). These Tregs were also more suppressive in males compared to females. Differences in Treg frequency were seen pre-puberty and were not altered by sex hormone treatment in GD individuals. However, Treg DEGs and functional transcriptomic pathways altered between post-pubertal males and females, including those involved in inflammatory signalling, overlapped with those altered by hormones in GD, suggesting hormones may also drive Treg functional changes. In addition, HDL metabolites modified by hormones showed differential associations with Treg phenotypes between post-pubertal males and females.Strikingly, sex differences in lipoproteins and Tregs were lost in JSLE, suggesting hormone signalling could be dysregulated in the pathogenesis of autoimmunity and could increase CVR for patients.Conclusion:Sex hormones drive altered lipoprotein metabolism and functional transcriptomic pathways in Tregs. Males have a lipoprotein profile associated with increased CVR, but a more anti-inflammatory immune profile compared to females. Together, this could explain sex differences in inflammatory disease susceptibilities and inform future sex-specific therapeutic strategies for the management of both JSLE and CVR.Acknowledgements:Lupus UKRosetrees TrustVersus ArthritisNIHR UCLH Biomedical Research CentreDisclosure of Interests:None declared

scholarly journals Pre-Transplant Immune Cell Function Assay as a Predictor of Early Cardiac Allograft Rejection

2021 ◽  
Vol 40 (4) ◽  
pp. S232-S233
Author(s):  
S.D. Maidman ◽  
C. Gidea ◽  
A. Reyentovich ◽  
S. Rao ◽  
T. Saraon ◽  
...  
Keyword(s):  
Allograft Rejection ◽  
Cell Function ◽  
Immune Cell ◽  
Cardiac Allograft ◽  
Immune Cell Function ◽  
Cardiac Allograft Rejection

scholarly journals Cellular and metabolic mechanisms of nutrient actions in immune function

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Philip Newsholme
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Vitamin D ◽  
Immune System ◽  
Cell Function ◽  
Immune Cell ◽  
Cell Structure ◽  
Nutritional Intervention ◽  
Immune Cell Function ◽  
And Function

AbstractVarious nutrients can change cell structure, cellular metabolism, and cell function which is particularly important for cells of the immune system as nutrient availability is associated with the activation and function of diverse immune subsets. The most important nutrients for immune cell function and fate appear to be glucose, amino acids, fatty acids, and vitamin D. This perspective will describe recently published information describing the mechanism of action of prominent nutritional intervention agents where evidence exists as to their action and potency.

Utility of an immune cell function assay to differentiate rejection from infectious enteritis in pediatric intestinal transplant recipients

2014 ◽  
Vol 28 (2) ◽  
pp. 229-235 ◽  
Author(s):  
Laura J. Wozniak ◽  
Robert S. Venick ◽  
Sherilyn Gordon Burroughs ◽  
Khiet D. Ngo ◽  
John P. Duffy ◽  
...  
Keyword(s):  
Cell Function ◽  
Immune Cell ◽  
Immune Cell Function ◽  
Transplant Recipients ◽  
Intestinal Transplant

Supplementation with Selenium Restores Age-Related Decline in Immune Cell Function

1995 ◽  
Vol 209 (4) ◽  
pp. 369-375 ◽  
Author(s):  
M. Roy ◽  
L. Kiremidjian-Schumacher ◽  
H. I. Wishe ◽  
M. W. Cohen ◽  
G. Stotzky
Keyword(s):  
Cell Function ◽  
Immune Cell ◽  
Immune Cell Function ◽  
Age Related

scholarly journals MMP-19 deficiency causes aggravation of colitis due to defects in innate immune cell function

2015 ◽  
Vol 9 (4) ◽  
pp. 974-985 ◽  
Author(s):  
R Brauer ◽  
J Tureckova ◽  
I Kanchev ◽  
M Khoylou ◽  
J Skarda ◽  
...  
Keyword(s):  
Cell Function ◽  
Immune Cell ◽  
Innate Immune ◽  
Innate Immune Cell ◽  
Immune Cell Function
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