scholarly journals Special Issue: “Skin Disease and Comorbidities”

2021 ◽  
Vol 10 (24) ◽  
pp. 5754
Author(s):  
Keiichi Yamanaka
Keyword(s):  
Inflammatory Cytokines ◽  
Systemic Inflammation ◽  
Skin Disease ◽  
Special Issue ◽  
Immune Systems ◽  
Immune Organs

The skin is one of the largest immune organs that involve innate and acquired immune systems, and is able to respond to internal and exogenous stimuli, producing a large amount of inflammatory cytokines, resulting in systemic inflammation [...]

scholarly journals Special Issue on Artificial Immune Systems: Theory and Applications

2007 ◽  
Vol 19 (4) ◽  
pp. 647-647
Author(s):  
Xiao-Zhi Gao ◽  
Mo-Yuen Chow ◽  
David Pelta ◽  
Jon Timmis
Keyword(s):  
Systems Theory ◽  
Artificial Immune Systems ◽  
Special Issue ◽  
Artificial Immune ◽  
Immune Systems

scholarly journals Conditional KCa3.1-Transgene Induction in Murine Skin Produces Pruritic Eczematous Dermatitis With Severe Epidermal Hyperplasia and Hyperkeratosis

2019 ◽  
Author(s):  
Javier Lozano-Gerona ◽  
Aida Oliván-Viguera ◽  
Pablo Delgado-Wicke ◽  
Vikrant Singh ◽  
Brandon M. Brown ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Skin Disease ◽  
Skin Condition ◽  
Pathological Features ◽  
Epidermal Hyperplasia ◽  
Potential Therapeutic Target ◽  
Epidermal Homeostasis ◽  
Eczematous Dermatitis ◽  
Selective Blocker ◽  
Pro Inflammatory Cytokines

ABSTRACTIon channels have recently attracted attention as potential mediators of skin disease. Here, we explored the consequences of genetically encoded induction of the cell volume-regulating Ca2+-activated KCa3.1 channel (Kcnn4) for murine epidermal homeostasis. Doxycycline-treated mice harboring the KCa3.1+-transgene under the control of the reverse tetracycline-sensitive transactivator (rtTA) showed 800-fold channel overexpression above basal levels in the skin and solid KCa3.1-currents in keratinocytes. This overexpression resulted in epidermal spongiosis, progressive epidermal hyperplasia and hyperkeratosis, itch and ulcers. The condition was accompanied by production of the pro-proliferative and pro-inflammatory cytokines, IL-β1 (60-fold), IL-23 (34-fold), IL-6 (33-fold), and TNFα (26-fold) in the skin. Treatment of mice with the KCa3.1-selective blocker, Senicapoc, significantly suppressed spongiosis and hyperplasia, as well as induction of IL-β1 (−88%), IL-23 (−77%), and IL-6 (−90%). In conclusion, KCa3.1-induction in the epidermis caused expression of pro-proliferative cytokines leading to spongiosis, hyperplasia and hyperkeratosis. This skin condition resembles pathological features of eczematous dermatitis and identifies KCa3.1 as a regulator of epidermal homeostasis and spongiosis, and as a potential therapeutic target.

scholarly journals Hyperphosphatemia Contributes to Inflammation and Iron Dysregulation in Models of Normal and Impaired Renal Function

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2238-2238
Author(s):  
Brian Czaya ◽  
Beatrice Richter ◽  
Christopher Yanucil ◽  
Isaac Campos ◽  
Kylie Heitman ◽  
...  
Keyword(s):  
Renal Function ◽  
Inflammatory Cytokines ◽  
Systemic Inflammation ◽  
Iron Metabolism ◽  
Impaired Renal Function ◽  
Conflicts Of Interest ◽  
Experimental Studies ◽  
Dependent Manner ◽  
Primary Mouse ◽  
Iron Dysregulation

Background Fibroblast growth factor (FGF) 23 is a phosphaturic hormone that targets the kidney to promote urinary phosphate excretion. In patients with chronic kidney disease (CKD), serum concentrations of phosphate (Pi) and FGF23 gradually increase as renal function declines and associate with various pathologies, including systemic inflammation and anemia. Our previous studies revealed FGF23 contributes to inflammation by directly targeting hepatocytes via FGF receptor 4 (FGFR4) and inducing phospholipase Cγ (PLCγ) signaling and the expression of inflammatory cytokines. Experimental studies have shown Pi can accelerate CKD-associated pathologies, but direct effects of Pi on the liver are not well described. Here we compare the effects of Pi versus FGF23 on hepatocytes and determine their respective contributions to inflammation and anemia in the context of CKD. Methods We subject mice with global deletion of FGFR4 and wild-type littermates to increasing dietary Pi load (0.7%, 2.0%, or 3.0%) or an adenine-rich diet (used as a CKD model) in order to examine systemic inflammation and alterations in iron metabolism in the setting of normal and impaired renal function. In addition, we study primary mouse hepatocytes treated with FGF23 and increasing Pi concentrations and examine the activation of downstream signaling events and expression levels of specific target genes. Furthermore, we determine if co-treatment with inhibitors of Pi uptake and downstream signal mediators block the observed effects. Results A 3% Pi diet as well as an adenine-rich diet promote inflammation and iron dysregulation in mice. These effects are exacerbated in FGFR4 knockout mice. In cultured hepatocytes, expression of inflammatory cytokines, hepcidin and FGF23 are induced by Pi in a dose-dependent manner. Furthermore, Pi activates NFkB signaling and the inhibition of Pi uptake and of NFkB protects from Pi-induced effects. Conclusion We postulate that in CKD, gradual elevations in serum Pi promote inflammation and anemia by targeting the liver to induce gene programs which regulate the inflammatory response and iron metabolism. Our study indicates these Pi effects may be independent of FGF23. Pharmacological approaches targeting hyperphosphatemia or hepatic Pi actions might alleviate various CKD-associated pathologies. Disclosures No relevant conflicts of interest to declare.

scholarly journals Are age-related biomarkers of dementia risk accelerated by low educational attainment?

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Katherine A. Schaefer ◽  
Frederick W. Unverzagt ◽  
Huiping Xu ◽  
Daniel O. Clark
Keyword(s):  
Inflammatory Cytokines ◽  
Systemic Inflammation ◽  
Neurofilament Light ◽  
Early Onset Dementia ◽  
Natural Logarithm ◽  
Age Related ◽  
Dementia Risk ◽  
Low Education ◽  
Anti Inflammatory ◽  
Young Old

Background: Low education significantly elevates dementia risk but it is not clear whether this is through chronic systemic inflammation, early-onset dementia pathology, or other factors. This project compares biomarkers of inflammation and dementia pathology in a young-old and older cohort.  Due to significantly lower education in the young-old cohort, we hypothesized evidence of similar or higher biomarker levels in the young-old cohort compared to the older cohort.   Methods: Blood samples were used to measure pro-inflammatory cytokines (C-reactive protein (CRP), tumor necrosis factor (TNF interleukin (IL)-6, and IL-1 anti-inflammatory cytokines (IL-10 and IL-1RA), and the brain biomarkers phosphorylated tau (p-tau) and neurofilament light (NfL). Inflammatory markers were measured at the Considine Lab at the Indiana University School of Medicine using ELISA assays while p-tau and NfL were measured with Simoa assays at the Quanterix lab in Massachusetts. We used the natural logarithm of all biomarker variables to address skewed data. Linear regression was used to investigate race- and gender-adjusted differences in the biomarkers.   Results: The young-old cohort (N=42) has a mean age of 62.4, 69.1% are female, and 78.6% are non-Hispanic black (NHB), while the older cohort (N=60) has a mean age of 80.3, 60% are female, and 20% are NHB. Median education in the young-old cohort is 12 vs 16 in the older cohort. Adjusted models showed higher mean CRP (p=0.004) and lower mean IL-10 (p<0.001) in the young-old cohort. TNF- (p <0.001), IL-6 (p=0.021), and IL-1(p=0.017), P-tau (p=0.003), and NfL (p<0.001) were all higher in the older cohort.   Conclusion: We found partial support of our hypothesis in that the younger, low education cohort had higher mean CRP and lower mean IL-10 (anti-inflammatory). However, brain biomarkers were higher in the older cohort. More research will be needed to determine if and how low education elevates ADRD risk through systemic inflammation.   

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