P1139EXPRESSION OF TOLL LIKE RECEPTORS, CELL ADHESION MOLECULES AND PRO-INFLAMMATORY CYTOKINES IN ESRD PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Mantabya Singh ◽  
Narayan Prasad ◽  
Nida Fatima ◽  
Amit Gupta ◽  
Chinmoy Sahu
Keyword(s):  
Cell Adhesion ◽  
Mrna Expression ◽  
Inflammatory Cytokines ◽  
Fungal Pathogens ◽  
Tnf Alpha ◽  
Rt Pcr ◽  
Cell Counts ◽  
Co Morbidity ◽  
Esrd Patients ◽  
Pro Inflammatory Cytokines

Abstract Background and Aims CAPD is well established modality of treatment for patients with end stage renal disease (ESRD). Peritonitis is a leading cause of technique failure and death in patients on CAPD. Studies on expressions of host factors like TLRs, CAMs and their relationship with inflammatory cytokines (IL-6, IL-12, TNF-alpha and IL-1 beta) involved in peritonitis and other co-morbidity and functional status are lacking throughout the world. Hence the present study has to be done to determine the expressions of TLR2 and TLR4, and CAMs in ESRD patients. To compare the expression of TLR2, TLR4, ICAM 1 and Pro-inflammatory cytokines (IL-6, IL-12, TNF-alpha and IL-1-beta) in Peritonitis, CAPD and CRF group patients. Method A total of 85 ESRD patients recruited and sub-divided into 3 groups. Group1- CAPD patient (n=25), Group 2- Peritonitis patient (n=30), and Group 3- CRF (n=30 patients). mRNA expression of TLR-2, TLR-4 were examined at gene levels by RT PCR and cell adhesion molecule (ICAM-1) were examined at gene and protein levels by RT PCR and ELISA respectively in Serum and Pro-inflammatory cytokines level were also examined by ELISA in serum. We performed microbiological culture for bacterial and fungal pathogens using automated BACTEC culture system. Cell counts were routinely done on every dialysate. Results Out of 30 samples of peritonitis group 15 were culture positive and 15 were culture negative. We found that in peritonitis group the mRNA expression of TLR-2 and TLR-4 was higher as compared to CRF (4.183±2.857vs 3.633±2.41) (p=0.049), (4.314±2.91vs 4.14±1.99) (p=0.015) and CAPD (4.183±2.857vs3.683±2.85) (p=0.041), (4.314±2.91vs 3.88±1.91) (p=0.009) respectively. At gene and protein level ICAM-1 was higher in peritonitis patient compared to CAPD (mRNA expression 4.76±2.64vs 4.36±3.48) (level in sera 660±201.2vs 514±157) (p=0.003). The IL-6 and IL-12 expression was higher in Peritonitis group as compared to CAPD (66.87±64.51vs214.35±220.05) (p=0.04) and (230.17±153.45vs417.04±302.96) (p=0.028) respectively. The TNF-alpha and IL-1-beta expression was not significant among the groups. Conclusion TLRs activation by bacterial molecules leads to the induction of cytokines (IL-6 and IL-12) and chemokine through the activation of NF-ķB pathway and may be responsible for atherosclerosis, morbidity and mortality in ESRD patients. Elevated level of ICAM-1, IL-6 and IL-12 may be responsible for chronic inflammation in Peritonitis group patients.

MO690HIGHER EXPRESSION OF TOLL LIKE RECEPTOR AND CELL ADHESION MOLECULES ARE ASSOCIATED WITH RECURRENT/RELAPSE PERITONITIS AND MORTALITY IN PATIENT ON CAPD

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Narayan Prasad ◽  
Nida Fatima ◽  
Mantabya Singh ◽  
Chinmoy Sahu
Keyword(s):  
Cell Adhesion ◽  
Statistical Analysis ◽  
Mrna Expression ◽  
Adhesion Molecules ◽  
Inflammatory Cytokines ◽  
Cell Adhesion Molecules ◽  
Morbidity And Mortality ◽  
Tnf Alpha ◽  
Co Morbidity ◽  
Esrd Patients

Abstract Background and Aims CAPD is an established modality of treatment for patients with end stage renal disease (ESRD). Peritonitis is a leading cause of technique failure and death in patients on CAPD. Studies on expressions of host genetic factors like TLRs, CAMs, Pro and Anti-inflammatory cytokines and their link to peritonitis and other co-morbidity and functional status are lacking throughout the world. Hence the present study was done to determine the expressions of TLR2 and TLR4, CAMs and inflammatory cytokines in patients on CAPD. Method A total of 110 ESRD patients categorized into 3 groups: 1- CAPD patients (n=45), group 2- CAPD with peritonitis patients (n=35), and group 3- CAPD patients with recurrent/relapsing peritonitis. (n=30) from department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Raebareli Road, Lucknow were included in the study. Blood sample was collected for analysis of cytokines and Cell adhesion molecules level and RNA extraction. Dialysate (only from patients undergoing PD with or without peritonitis)- whole drained bag; 50-100 ml for microscopy and culture for bacterial and fungal pathogens using automated BACTEC culture system in patients with peritonitis and supernatant was collected for cytokine ELISA. Statistical analysis: One-way ANOVA (Two tailed) and non-parametric student t-test used for statistical analysis of differences between the group. Results mRNA expression of TLR 2 and TLR 4 expression was higher in peritonitis and recurrent/relapsing peritonitis group as compared to CAPD patient without peritonitis group. mRNA expression of TNF-alpha, IL-1B and IFN-gamma was higher in peritonitis group of patients compared to all other group of patients. mRNA expression of IL-10 and IL-4 was also highest in Peritonitis group. Level of IL-1β and TNF-alpha was observed to be elevated in peritonitis and recurrent/relapse peritonitis patients compared to CAPD in sera and dialysate. IL-12 level in Sera was also elevated in peritonitis patients but its level in dialysate was highest in CAPD without peritonitis as compared to peritonitis and recurrent/relapse. IL-10 and IL-4 was observed to be elevated in peritonitis group followed by CAPD with recurrent/relapse peritonitis in sera whereas in dialysate level of IL-4 was higher in both peritonitis group and Recurrent groups of patients but IL-10 level was highest in peritonitis group but less in recurrent/relapse. mRNA Expression levels of adhesion molecule ICAM-1 and LFA-1 were observed to be higher in Peritonitis and Recurrent groups as compared to the CAPD without peritonitis; whereas, in sera the level of ICAM-1 was higher in peritonitis patients. However, in dialysate its level was observed to be almost similar. Level of LFA-1 was observed to be higher in peritonitis group in dialysate but in sera its level was higher in Recurrent group with peritonitis. Conclusion It is likely that CAMs are also involved in the pathogenesis of CAPD peritonitis, its morbidity and mortality. TLRs activation by bacterial molecules leads to the induction of chemokines and cytokines through the activation of NF-ķB pathway and may be responsible for atherosclerosis, morbidity, and mortality in ESRD patients. Elevated level of ICAM-1, IL-1beta, TNF-a and IFN-G may be responsible for chronic inflammation in PD patients.

Molecular Biocompatibility Evaluation of Poly-L-Ornithine-Coated Alginate Microcapsules by Investigating mRNA Expression of Pro-Inflammatory Cytokines

2012 ◽  
Vol 14 ◽  
pp. 53-64 ◽  
Author(s):  
Ai Zheng Chen ◽  
Yan Bai ◽  
Shi Bin Wang ◽  
Yuan Gang Liu ◽  
Zong Xiang Chen
Keyword(s):  
Mrna Expression ◽  
Inflammatory Cytokines ◽  
Molecular Level ◽  
Alginate Beads ◽  
Positive Control ◽  
Rt Pcr ◽  
Coating Materials ◽  
Time Part ◽  
Pcr Method ◽  
Pro Inflammatory Cytokines

Following a polyelectrolytical complex reaction, the poly-L-ornithine (PLO)-alginate microcapsules were prepared by coating PLO on calcium alginate beads which were produced by a high-voltage electrostatic droplet generator. The biocompatibility of the microcapsules at the molecular level was evaluated through investigating the mRNA expression of pro-inflammatory cytokines; that is, the effect of the PLO coating of alginate beads on the mRNA expression of TNF-α, IL-1β, and IL-6 were measured using the RT-PCR method. The resulting PLO-coated alginate microcapsules have a smooth surface with a mean diameter of 309µm. The molecular biocompatibility studies show that coating microcapsules with PLO has no significant effect on the biocompatibility of alginate microcapsules (p>0.05), and both alginate microcapsules and PLO-coated microcapsules are significantly different from the positive control (p<0.05); however, both are also capable of causing an inflammatory response at a molecular level since both are significantly different from the blank control (p<0.05). Furthermore, with the increase in concentration of microcapsules or co-cultured time, part of the mRNA expression of cytokines is significantly increased. The results also demonstrate that the method used in this study, co-incubating the microcapsules with macrophages and measuring the mRNA expression of cytokines by RT-PCR, may be a useful method for evaluating the biocompatibility of coating materials of microcapsules.

scholarly journals Inflammatory Cytokine Expressions of the Subacromial Bursitis and Glenohumeral Joint Synovitis in the Patients with Full Thickness Rotator Cuff Tear

1970 ◽  
Vol 14 (2) ◽  
pp. 172-178 ◽  
Author(s):  
Sung Kyu Kim ◽  
Hyung Nam Kim ◽  
Eun Sun Moon ◽  
Keun Young Lim ◽  
Nam Young Cho ◽  
...  
Keyword(s):  
Rotator Cuff ◽  
Mrna Expression ◽  
Inflammatory Cytokines ◽  
Glenohumeral Joint ◽  
Expression Patterns ◽  
Tnf Alpha ◽  
Full Thickness ◽  
Rt Pcr ◽  
Polymerase Chain ◽  
Cox 1

PURPOSE: The purpose of this study was to compare expression patterns of inflammatory cytokines between subacromial bursitis and glenohumeral (GH) joint synovitis in full thickness rotator cuff (RC) tear patients with severe pain.MATERIALS AND METHODS: We were able to obtain enough tissue from nine subacromial bursitis and GH synovitis patients at the same time during surgery and evaluate them. We compared mRNA expression of inflammatory cytokines between the two groups using Reverse Transcription-Polymerase Chain Reaction (RT-PCR).RESULTS: Relative mean mRNA expression of IL-1beta, IL-6, TNF-alpha, COX-1, COX-2 and SDF-1 in the tissues of subacromial bursitis and GH synovitis patients did not show significant differences.CONCLUSION: GH synovitis may be another source of shoulder pain with subacromial bursitis in full thickness RC tear patients with severe pain.

scholarly journals Cystine reduces tight junction permeability and intestinal inflammation induced by oxidative stress in Caco-2 cells

Amino Acids ◽  
2021 ◽  
Author(s):  
Tatsuya Hasegawa ◽  
Ami Mizugaki ◽  
Yoshiko Inoue ◽  
Hiroyuki Kato ◽  
Hitoshi Murakami
Keyword(s):  
Oxidative Stress ◽  
Tight Junction ◽  
Mrna Expression ◽  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Intestinal Barrier ◽  
Barrier Dysfunction ◽  
Whole Cells ◽  
Intestinal Barrier Dysfunction ◽  
Pro Inflammatory Cytokines

AbstractIntestinal oxidative stress produces pro-inflammatory cytokines, which increase tight junction (TJ) permeability, leading to intestinal and systemic inflammation. Cystine (Cys2) is a substrate of glutathione (GSH) and inhibits inflammation, however, it is unclear whether Cys2 locally improves intestinal barrier dysfunction. Thus, we investigated the local effects of Cys2 on oxidative stress-induced TJ permeability and intestinal inflammatory responses. Caco-2 cells were cultured in a Cys2-supplemented medium for 24 h and then treated with H2O2 for 2 h. We assessed TJ permeability by measuring transepithelial electrical resistance and the paracellular flux of fluorescein isothiocyanate–dextran 4 kDa. We measured the concentration of Cys2 and GSH after Cys2 pretreatment. The mRNA expression of pro-inflammatory cytokines was assessed. In addition, the levels of TJ proteins were assessed by measuring the expression of TJ proteins in the whole cells and the ratio of TJ proteins in the detergent-insoluble fractions to soluble fractions (IS/S ratio). Cys2 treatment reduced H2O2-induced TJ permeability. Cys2 did not change the expression of TJ proteins in the whole cells, however, suppressed the IS/S ratio of claudin-4. Intercellular levels of Cys2 and GSH significantly increased in cells treated with Cys2. Cys2 treatment suppressed the mRNA expression of pro-inflammatory cytokines, and the mRNA levels were significantly correlated with TJ permeability. In conclusion, Cys2 treatment locally reduced oxidative stress-induced intestinal barrier dysfunction possively due to the mitigation of claudin-4 dislocalization. Furthermore, the effect of Cys2 on the improvement of intestinal barrier function is related to the local suppression of oxidative stress-induced pro-inflammatory responses.

TNF-alpha stimulates activation of pro-MMP2 in human skin through NF-(kappa)B mediated induction of MT1-MMP

2001 ◽  
Vol 114 (1) ◽  
pp. 131-139 ◽  
Author(s):  
Y.P. Han ◽  
T.L. Tuan ◽  
H. Wu ◽  
M. Hughes ◽  
W.L. Garner
Keyword(s):  
Gene Expression ◽  
Wound Healing ◽  
Human Skin ◽  
Inflammatory Cytokines ◽  
Intracellular Signaling ◽  
Chronic Wounds ◽  
Dermal Fibroblasts ◽  
Tnf Alpha ◽  
Nf Kappa B ◽  
Pro Inflammatory Cytokines

Tumor necrosis factor-alpha (TNF-(alpha)) is an important mediator during the inflammatory phase of wound healing. Excessive amounts of pro-inflammatory cytokines such as TNF-(alpha) are associated with inflammatory diseases including chronic wounds. Matrix metalloproteinases (MMPs) are involved in matrix re-modeling during wound healing, angiogenesis and tumor metastasis. As with pro-inflammatory cytokines, high levels of MMPs have been found in inflammatory states such as chronic wounds. In this report we relate these two phenomena. TNF-(alpha) stimulates secretion of active MMP-2, a type IV collagenase, in organ-cultured full-thickness human skin. This suggests a mechanism whereby excess inflammation affects normal wound healing. To investigate this observation at the cellular and molecular levels, we examined TNF-(alpha) mediated activation of pro-MMP-2, induction of MT1-MMP, and the intracellular signaling pathways that regulate the proteinase in isolated human dermal fibroblasts. We found that TNF-(alpha) substantially promoted activation of pro-MMP-2 in dermal fibroblasts embedded in type-I collagen. In marked contrast, collagen or TNF-(alpha) individually had little influence on the fibroblast-mediated pro-MMP-2 activation. One well-characterized mechanism for pro-MMP-2 activation is through a membrane type matrix metalloproteinase, such as MT1-MMP. We report that TNF-(alpha) significantly induced MT1-MMP at the mRNA and protein levels when the dermal fibroblasts were grown in collagen. Although the intracellular signaling pathway regulating mt1-mmp gene expression is still obscure, both TNF-(alpha) and collagen activate the NF-(kappa)B pathway. In this report we provide three sets of evidence to support a hypothesis that activation of NF-(kappa)B is essential to induce MT1-MMP expression in fibroblasts after TNF-(alpha) exposure. First, SN50, a peptide inhibitor for NF-(kappa)B nuclear translocation, simultaneously blocked the TNF-(alpha) and collagen mediated MT1-MMP induction and pro-MMP-2 activation. Secondly, TNF-(alpha) induced I(kappa)B to breakdown in fibroblasts within the collagen lattice, a critical step leading to NF-(kappa)B activation. Lastly, a consensus binding site for p65 NF-(kappa)B (TGGAGCTTCC) was found in the 5′-flanking region of human mt1-mmp gene. Based on these results and previous reports, we propose a model to explain TNF-(alpha) activation of MMP-2 in human skin. Activation of NF(kappa)B signaling in fibroblasts embedded in collagen induces mt1-mmp gene expression, which subsequently activates the pro-MMP-2. The findings provide a specific mechanism whereby TNF-(alpha) may affect matrix remodeling during wound healing and other physiological and pathological processes.

scholarly journals Dose-dependent immune response in milk cells and mammary tissue after intramammary administration of lipopolysaccharide in dairy cows

2008 ◽  
Vol 52 (No. 6) ◽  
pp. 231-244 ◽  
Author(s):  
C. Werner-Misof ◽  
M.W. Pfaffl ◽  
R.M. Bruckmaier
Keyword(s):  
Immune Response ◽  
Mrna Expression ◽  
Real Time ◽  
Polymorphonuclear Neutrophils ◽  
Mammary Tissue ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Lps Challenge ◽  
Cell Counts ◽  
Cox 2

The immune response in milk cells and the status of mammary tight junctions (TJ) in response to intramammary (IM) infusion of different doses of <i>Escherichia col</i>i lipopolysaccharide (LPS) was investigated. <i>Experiment I</i>: Seven German Braunvieh cows were IM infused into one quarter with 1 &mu;g (LPS-1) and 3 &mu;g (LPS-3) of LPS, respectively, and the contralateral control quarter with saline (9 g/l; C). Milk samples were taken immediately before and 12, 24, 36, 48, 60, 84 and 108 h after infusion and analysed for somatic cell counts (SCC), lactose, sodium (Na) and chloride (Cl) ions, and electrical conductivity (EC). Milk cell mRNA expression of various inflammatory factors was quantified by real-time RT-PCR. Blood samples were taken immediately after milking for the analysis of leukocytes (WBC), polymorphonuclear neutrophils (PMN), Na and Cl. Milk SCC, lactose, Na, Cl and EC did not differ significantly between LPS-1 and C quarters after the challenge. In LPS-3 quarters SCC levels increased within the first 12 h, reached peak levels between 12 and 36 h (<i>P</i> &le; 0.001) and decreased (<i>P</i> &le; 0.05) thereafter to reach baseline at 108 hours. Lactose in LPS-3 quarters decreased (<i>P</i> &le; 0.05) to a minimum at 24 h and increased slightly thereafter while EC, Na, and Cl increased transiently in response to LPS-3. WBC and PMN levels in both groups decreased numerically within 24 h after LPS administration. In LPS-1, WBC at 24, 48 and 108 h were significantly lower whereas in LPS-3 they were significantly higher than at time 0. TNF&alpha;-mRNA expression in both groups did not change in response to IM LPS-challenge. IL-1&beta;-mRNA expression at 12, 24 and 36 h in LPS-1 quarters increased significantly as compared to time 0. In LPS-3 quarters the mRNA expression values of all tested ILs increased significantly as compared to time 0 within 12 h after LPS-challenge. IL-1&beta;-mRNA expression decreased (<i>P</i> &le; 0.05) at 48 and 84 h in LPS quarters. IL-8 mRNA was significantly decreased at 84 h after challenge in LPS-3 quarters. COX-2-mRNA expression in LPS-1 quarters decreased significantly as compared to time 0 at 48, 84 and 108 h, with a minimum at 84 h (<i>P</i> &le; 0.05). In LPS-3 quarters COX-2-mRNA levels increased (<i>P</i> &le; 0.05) within 48 h after the LPS-challenge. <i>Experiment II</i>: Six cows (5 German Braunvieh, 1 Brown Swiss) were injected in one quarter with 100 &mu;g LPS and in the contralateral quarter with saline (9 g/l; C). Mammary biopsy samples of both quarters were taken immediately before and at 3, 6, 9 and 12 h after infusion and mRNA expression of TJ proteins occludin (OCLN) and zonula occludens (ZO-) 1, 2 and 3 were quantified by real-time RT-PCR. OCLN-mRNA expression did not change in response to the IM infusion while that of ZO-1, ZO-2 and ZO-3 decreased significantly within six hours. In conclusion, a dose of 1 &mu;g LPS did not initiate a immune response in the mammary gland. Furthermore the dose of 100 &mu;g of LPS enhanced TJ permeability by reducing TJ plaque proteins density.

scholarly journals Effect of chronic oxytocin-treatment on the bovine mammary gland immune system

2008 ◽  
Vol 52 (No. 11) ◽  
pp. 475-486 ◽  
Author(s):  
C. Werner-Misof ◽  
M.W. Pfaffl ◽  
H.H.D. Meyer ◽  
R.M. Bruckmaier
Keyword(s):  
Mammary Gland ◽  
Immune System ◽  
Mrna Expression ◽  
Real Time ◽  
Mammary Tissue ◽  
Rt Pcr ◽  
Milk Samples ◽  
Cell Counts ◽  
Group 6 ◽  
Cox2 Expression

The aim of this study was to evaluate the effect of chronic oxytocin (OT) treatment on the mammary gland immune system. In <I>Experiment I</I> fourteen healthy cows were used to study the effect of chronic intramuscular (im) OT administration on concentration of milk somatic cells and white blood cells (WBC). Cows in the OT-group (6) were im injected with 50 IU OT (5 ml) whereas animals of the C-group (6) were im injected with 5 ml of saline (9 g/l) for eight days (Day 1–8) before each milking. Milk samples were taken during normal milking time on Day 0–3, 5, 7, 9–11 and 18. Blood samples were taken immediately after each milking and analysed for WBC count, polymorphonuclear neutrophils, potassium (K), sodium (Na) and chloride (Cl) ions, and blood lactose. All milk samples were analysed for somatic cell counts (SCC), lactose, Na, Cl and electrical conductivity (EC). Furthermore mRNA expression of tumor necrosis factor-&alpha; (TNF&alpha;), interleukin (IL)-1&beta;, IL-6, IL-8 and cyclooxygenase-2 (COX2) in milk cells were measured via real-time RT-PCR. None of the investigated milk and blood parameters changed significantly in response to the OT treatment. The mRNA-expression of TNF&alpha; decreased (<I>P</I> < 0.05) to a minimum on Day 3 in response to OT administration. IL-1&beta; and IL-6-mRNA expression decreased (<I>P</I> < 0.05) to a minimum within three day. IL-8 and COX2 expression did not change in response to OT treatment. In <I>Experiment II</I> twelve cows, randomly divided into two groups of six, were used to investigate the effect of chronic im OT administration on mammary tissue. Cows were im administered 50 IU OT (OT-group) or 5 ml saline (9 g/l; C-group) before each milking during eight days. Biopsy samples were taken after every morning milking. The mRNA expression of various inflammatory factors and the tight junction (TJ) proteins occludin (OCLN) and zonula occludens (ZO)-1, ZO-2 and ZO-3 were measured via real-time RT-PCR. TNF&alpha;-mRNA expression decreased (Day 2 with <I>P</I> < 0.05) within the first four days of OT administration and increased (<I>P</I> < 0.05) in the C-group on Day 2. IL-1&beta; expression levels of the OT-group increased transiently and decreased on Day 3 and in the C-group values increased significantly on Day 3 as compared to Day 0. IL-6 expression in the OT-group decreased (<I>P</I> < 0.05) to a minimum on Day 1 and increased (<I>P</I> < 0.05) as compared to Day 0 on Day 7 and increased significantly on Day 1 and Day 5 compared to Day 0 in group C. IL-8 and COX2 expression did not change in response to OT administration. The mRNA-expression of OCLN and ZO-3 decreased (<I>P</I> < 0.05) as compared to Day 0 with a minimum on Day 7. ZO-1 and ZO-2 expression did not change due to OT administration. ZO-2-mRNA expression in C-group decreased significantly on Day 2 compared to Day 0. In conclusion, chronic OT administration induced increasing SCC and EC levels in milk as well as K and lactose in blood while nearly all investigated cytokines in milk cells and mammary tissue were down regulated. The mRNA expressions of the TJ proteins OCLN and ZO-3 were down-regulated in response to the OT treatment what indicates an increasing TJ permeability. Besides the effect on TJ proteins there was no obvious change of the immunological competence of the mammary gland in response to OT. However, a more complete milk ejection should help to remove pathogens during milking.

Inflammation as the Common Biological Link Between Depression and Cardiovascular Diseases: Can Carnosine Exert a Protective Role?

2020 ◽  
Vol 27 (11) ◽  
pp. 1782-1800 ◽  
Author(s):  
Giuseppe Caruso ◽  
Claudia G. Fresta ◽  
Margherita Grasso ◽  
Rosa Santangelo ◽  
Giuseppe Lazzarino ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Diseases ◽  
Inflammatory Cytokines ◽  
Macrophage Polarization ◽  
Antioxidant Properties ◽  
Reactive Species ◽  
Inflammatory Status ◽  
Co Morbidity ◽  
The Common ◽  
Pro Inflammatory Cytokines

: Several epidemiological studies have clearly shown the high co-morbidity between depression and Cardiovascular Diseases (CVD). Different studies have been conducted to identify the common pathophysiological events of these diseases such as the overactivation of the hypothalamic- pituitary-adrenal axis and, most importantly, the dysregulation of immune system which causes a chronic pro-inflammatory status. The biological link between depression, inflammation, and CVD can be related to high levels of pro-inflammatory cytokines, such as IL-1β, TNF-α, and IL-6, released by macrophages which play a central role in the pathophysiology of both depression and CVD. Pro-inflammatory cytokines interfere with many of the pathophysiological mechanisms relevant to depression by upregulating the rate-limiting enzymes in the metabolic pathway of tryptophan and altering serotonin metabolism. These cytokines also increase the risk to develop CVD, because activation of macrophages under this pro-inflammatory status is closely associated with endothelial dysfunction and oxidative stress, a preamble to atherosclerosis and atherothrombosis. : Carnosine (β-alanyl-L-histidine) is an endogenous dipeptide which exerts a strong antiinflammatory activity on macrophages by suppressing reactive species and pro-inflammatory cytokines production and altering pro-inflammatory/anti-inflammatory macrophage polarization. This dipeptide exhibits antioxidant properties scavenging reactive species and preventing oxidative stress-induced pathologies such as CVD. : In the present review we will discuss the role of oxidative stress and chronic inflammation as common pathophysiological events both in depression and CVD and the preclinical and clinical evidence on the protective effect of carnosine in both diseases as well as the therapeutic potential of this dipeptide in depressed patients with a high co-morbidity of cardiovascular diseases.

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