scholarly journals β-Sitosterol Alters the Inflammatory Response in CLP Rat Model of Sepsis by Modulation of NFκB Signaling

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Sara Kasirzadeh ◽  
Mohammad Hossein Ghahremani ◽  
Neda Setayesh ◽  
Fereshteh Jeivad ◽  
Amir Shadboorestan ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Bacterial Infections ◽  
Sham Group ◽  
Cecal Ligation ◽  
Serum Levels ◽  
Protective Role ◽  
Mrna Levels ◽  
Tnf Α ◽  
Male Wistar Rats ◽  
Host Inflammatory Response

Purpose. Sepsis originates from the host inflammatory response, especially to bacterial infections, and is considered one of the main causes of death in intensive care units. Various agents have been developed to inhibit mediators of the inflammatory response; one prospective agent is β-sitosterol (βS), a phytosterol with a structure similar to cholesterol. This study is aimed at evaluating the effects of βS on the biomarkers of inflammation and liver function in cecal ligation and puncture- (CLP-) induced septic rats. Methods. Thirty male Wistar rats were divided equally into six groups as follows: sham, CLP, CLP+dexamethasone (DX, 0.2 mg/kg), CLP+βS (1 mg/kg), CLP+imipenem (IMI, 20 mg/kg), and CLP+IMI (20 mg/kg)+βS (1 mg/kg). Serum levels of IL-1β, IL-6, IL-10, AST, ALT, and liver glutathione (GSH) were assessed by ELISA. Liver expression levels of TNF-α and NF-κBi mRNAs were evaluated by RT-qPCR. Results. Serum concentrations of IL-1β, IL-6, IL-10, ALT, and AST and mRNA levels of TNF-α and NF-κBi were all significantly higher in septic rats than in normal rats ( p < 0.05 ). Liver GSH content was markedly lower in the CLP group than that in the sham group. βS-treated rats had remarkably lower levels of IL-1β, IL-6, IL-10, TNF-α, NF-κBi, AST, and ALT (51.79%, 62.63%, 41.46%, 54.35%, 94.37%, 95.30%, 34.87%, and 46.53% lower, respectively) and greater liver GSH content (35.71% greater) compared to the CLP group ( p < 0.05 ). Conclusion. βS may play a protective role in the septic process by mitigating inflammation. This effect is at least partly mediated by inhibition of the NF-κB signaling pathway. Thus, βS can be considered as a supplementary treatment in septic patients.

scholarly journals Danshensu inhibits the IL-1β-induced inflammatory response in chondrocytes and osteoarthritis possibly via suppressing NF-κB signaling pathway

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Zhixian Xu ◽  
Tie Ke ◽  
Yongfa Zhang ◽  
Licheng Guo ◽  
Feng Chen ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathway ◽  
Protective Role ◽  
Cell Counting ◽  
Inos Mrna ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Tnf Α ◽  
Cox 2

Abstract Purpose Osteoarthritis (OA) is the most common inflammatory disease associated with pain and cartilage destruction. Interleukin (IL)-1β is widely used to induce inflammatory response in OA models. This study aimed to explore the role of Danshensu (DSS) in IL-1β-induced inflammatory responses in OA. Methods IL-1β was used to induce chondrocyte inflammation. Cell viability was evaluated by Cell Counting Kit-8 (CCK-8) assay. IL-6, COX-2, TNF-α, and iNOS mRNA levels were detected by qRT-PCR. MMP3, MMP13, ADAMTS4, ADAMTS5, Aggrecan, Collagen, p-IκBα, and p-p65 protein levels were detected by Western blot. An OA mouse model was established by surgical destabilization of the medial meniscus (DMM), and the Osteoarthritis Research Society International (OARSI) score was evaluated by H&E staining. Results DSS did not affect the levels of inflammatory indicators including IL-6, COX-2, TNF-α, iNOS, PEG2, and NO but suppressed COX-2 and iNOS protein expression in IL-1β treated chondrocytes. In addition, DSS downregulated IL-1β-enhanced expression of MMP3, MMP13, ADAMTS4, and ADAMTS5 and upregulated aggrecan and collagen expression. Moreover, DSS significantly inhibited IL-1β-induced phosphorylation of p-IκBα and p-p65 in a dose-dependent manner in chondrocytes, suggesting it plays a role in the NF-κB signaling pathway. Furthermore, DSS significantly reduced DMM-induced cartilage OARSI score in mice, further demonstrating its protective role in OA progression in vivo. Conclusions Our study revealed the protective role of DSS in OA, suggesting that DSS might act as a potential treatment for OA.

scholarly journals AB0713 PERIODONTAL DISEASES AND ITS ASSOCIATION WITH ANKYLOSING SPONDYLITIS/SPA: A SYSTEMATIC REVIEW

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1652.1-1652
Author(s):  
A. Pandey ◽  
V. Ravindran ◽  
M. Pandey ◽  
R. Rajak ◽  
V. Pandey
Keyword(s):  
Systematic Review ◽  
Ankylosing Spondylitis ◽  
Connective Tissue ◽  
Inflammatory Response ◽  
Periodontal Disease ◽  
Close Association ◽  
Case Control ◽  
Clinical Attachment Loss ◽  
Tnf Α ◽  
Host Inflammatory Response

Background:A close association between periodontal disease and Ankylosing spondylitis (AS) has long been specualted. Both diseases are characterized by dysregulation of the host inflammatory response, leading to further destruction of soft and hard connective tissue with there being evidence of increased levels of TNF-α and various interleukins in both patients of AS and periodontitis.Objectives:The aim of this systematic review was to appraise the available literature exploring the relationship between AS and periodontal disease.Methods:We searched Medline & Embase databases (from their inception till October 2019) using appropriate combinations of following search items with limits ‘(English, Human)’; Ankylosing spondylitis, spondyloarthritis, spondyloarthropathies, spondyloarthritides, spinal disease, musculoskeletal disease, Rheumatic disease AND periodontitis, periodontal disease, periodontoses, parodontoses, chronic periodontitis, gum disease, gingivitis, oral health, dental health, plaque index, bleeding on probing, probing pocket depth, clinical attachment loss. This search was supplemented by the manual search of bibliographies of articles selected and conferences proceedings of EULAR. Only be reviews, observational study of cross-sectional, cohort or case control type on adult patients with AS were selected. Data was extracted from a predesigned proforma. A close association between periodontal disease and Ankylosing spondylitis (AS) has long been specualted. Both diseases are characterized by dysregulation of the host inflammatory response, leading to further destruction of soft and hard connective tissue with there being evidence of increased levels of TNF-α and various interleukins in both patients of AS and periodontitis.Results:A total number of 984 articles were identified and 12 were selcted for detailed appraisal (Figure 1, PRISMA flow chart). They were all case control studies. The prevalence of periodontitis ranged from 38% to 88% in patients with AS whereas in the control group from 26% to 71 % in controls. Out of 12 studies, two showed significant changes in Plaque Index (PI), two studies showed altered Pocket Probing Depth (PPD), three showed significant increased in Clinical Attachment Loss (CAL) and increased Bleeding On Probing (BOP) was seen in 2 studies. In 7 studies, periodontitis was seen in a significant number of patients with AS (P<0.05). All studies reported that the prevalence of periodontal disease in AS patients was higher as compared to non-AS patients.Conclusion:Our systematic review found an association between AS and periodontal disease. Patients with AS show higher prevalence of periodontitis and a poor oral hygiene as compared to healthy controls. At practice level, this systematic review underscores the need for a collaboration between dentists and rheumatologist.Disclosure of Interests:None declared

scholarly journals Comparing the protective effects of resveratrol, curcumin and sulforaphane against LPS/IFN-γ-mediated inflammation in doxorubicin-treated macrophages

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Haidy A. Saleh ◽  
Eman Ramdan ◽  
Mohey M. Elmazar ◽  
Hassan M. E. Azzazy ◽  
Anwar Abdelnaser
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Response ◽  
Raw 264.7 Cells ◽  
Inos Mrna ◽  
No Production ◽  
Raw 264.7 ◽  
Mrna Levels ◽  
Protective Effects ◽  
Tnf Α ◽  
Ifn Γ

AbstractDoxorubicin (DOX) chemotherapy is associated with the release of inflammatory cytokines from macrophages. This has been suggested to be, in part, due to DOX-mediated leakage of endotoxins from gut microflora, which activate Toll-like receptor 4 (TLR4) signaling in macrophages, causing severe inflammation. However, the direct function of DOX on macrophages is still unknown. In the present study, we tested the hypothesis that DOX alone is incapable of stimulating inflammatory response in macrophages. Then, we compared the anti-inflammatory effects of curcumin (CUR), resveratrol (RES) and sulforaphane (SFN) against lipopolysaccharide/interferon-gamma (LPS/IFN-γ)-mediated inflammation in the absence or presence of DOX. For this purpose, RAW 264.7 cells were stimulated with LPS/IFN-γ (10 ng/mL/10 U/mL) in the absence or presence of DOX (0.1 µM). Our results showed that DOX alone is incapable of stimulating an inflammatory response in RAW 264.7 macrophages. Furthermore, after 24 h of incubation with LPS/IFN-γ, a significant increase in tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS) mRNA levels was observed. Similarly, nitric oxide (NO) production and TNF-α and IL-6 protein levels were significantly upregulated. Moreover, in LPS/IFN-γ-treated macrophages, the microRNAs (miRNAs) miR-146a, miR-155, and miR-21 were significantly overexpressed. Interestingly, upon testing CUR, RES, and SFN against LPS/IFN-γ-mediated inflammation, only SFN was able to significantly reverse the LPS/IFN-γ-mediated induction of iNOS, TNF-α and IL-6 and attenuate miR-146a and miR-155 levels. In conclusion, SFN, at the transcriptional and posttranscriptional levels, exhibits potent immunomodulatory action against LPS/IFN-γ-stimulated macrophages, which may indicate SFN as a potential treatment for DOX-associated inflammation.

scholarly journals Carbohydrate response element binding protein (ChREBP) modulates the inflammatory response of mesangial cells in response to glucose

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Yan Chen ◽  
Yan-Jun Wang ◽  
Ying Zhao ◽  
Jin-Cheng Wang
Keyword(s):  
Diabetes Mellitus ◽  
Inflammatory Response ◽  
Mesangial Cells ◽  
Binding Protein ◽  
The Body ◽  
Mrna Levels ◽  
Diabetic Mice ◽  
Response Element ◽  
Tnf Α ◽  
Element Binding Protein

Diabetic nephropathy (DN) is one of the most devastating complications of diabetes mellitus. Carbohydrate response element binding protein (ChREBP) is a basic helix–loop–helix leucine zipper transcription factor that primarily mediates glucose homeostasis in the body. The present study investigated the role of ChREBP in the pathogenesis of DN. The expression of ChREBP was detected in patients with type 2 diabetes mellitus (T2DM), diabetic mice, and mesangial cells. ELISA was used to measure cytokine production in mesangial cells. Flow cytometry analysis was performed to detect the apoptosis of mesangial cells in the presence of high glucose. The expression levels of ChREBP and several cytokines (TNF-α, IL-1β, and IL-6) were up-regulated in T2DM patients. The mRNA and protein levels of ChREBP were also significantly elevated in the kidneys of diabetic mice. Moreover, glucose treatment promoted mRNA levels of TNF-α, IL-1β, and IL-6 in mesangial cells. Glucose stimulation induced significant apoptosis of SV40 MES 13 cells. In addition, transfection with ChREBP siRNA significantly inhibited ChREBP expression. Consequently, the inflammatory responses and apoptosis were inhibited in SV40 MES 13 cells. These results demonstrated that ChREBP could mediate the inflammatory response and apoptosis of mesangial cells, suggesting that ChREBP may be involved in the pathogenesis of DN.

scholarly journals Inhibition of NF-κB by Pyrrolidine Dithiocarbamate Prevents the Inflammatory Response in a Ligature-Induced Peri-Implantitis Model: A Canine Study

2018 ◽  
Vol 49 (2) ◽  
pp. 610-625 ◽  
Author(s):  
Chun-Yan He ◽  
Li-Peng Jiang ◽  
Cheng-Yue Wang ◽  
Yue Zhang
Keyword(s):  
Inflammatory Response ◽  
Protein Expression ◽  
Quantitative Polymerase Chain Reaction ◽  
Pyrrolidine Dithiocarbamate ◽  
Mrna Levels ◽  
Periodontal Ligament Fibroblasts ◽  
Necrosis Factor Alpha ◽  
Periodontal Tissues ◽  
Periodontal Inflammation ◽  
Tnf Α

Background/Aims: The roles of toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) in peri-implantitis are unclear. Here, we used a canine model of peri-implantitis to explore the effects of inhibiting NF-κB with pyrrolidine dithiocarbamate (PDTC) on the inflammatory response in ligature-induced peri-implantitis. Methods: After successfully establishing the peri-implantitis model, beagles were randomly assigned to normal, model or PDTC groups. ELISA tests were used to determine the levels of interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor alpha (TNF-α). Immunohistochemistry was employed to assess the expression of NF-κB p65. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine the mRNA levels of TLR4 and NF-κB p65, and western blot analysis was used to measure the protein levels of TLR4 in periodontal tissues from each group. Periodontal ligament fibroblasts (PDLFs) were cultured and subsequently classified into PDLF normal, PDLF model, PDLF LPS, PDLF PDTC, and PDLF LPS + PDTC groups. An immunofluorescence assay was used to measure the expression level of NF-κB p65. The CCK-8 assay and flow cytometry were performed to evaluate cell proliferation and apoptosis. Results: The in vitro results indicated that NF-κB p65 and TLR4 were upregulated in canine periodontal tissues, and PDTC could suppress the expression levels of NF-κB p65 and TLR4. Inflammation could increase TLR4 protein expression in canine periodontal tissue, and PDTC could inhibit the inflammation-induced increase in TLR4 protein expression. These results revealed that PDTC could reverse the LPS-induced increases in the levels of IL-1, IL-6, IL-8 and TNF-α. In vivo, the results demonstrated that PDTC inhibited the LPS-induced NF-κB p65 upregulation, and PDTC could reverse the inhibitory effect of the PDLF model + LPS on the proliferation of periodontal fibroblasts. The results also showed that in the PDLF model, LPS promoted PDLF apoptosis by inducing implant periodontitis in canines, but PDTC inhibited the PDLF apoptosis and relieved implant periodontitis in canines. Conclusion: Based on our results, we concluded that PDTC can inhibit the expression of NF-κB and alleviate the inflammatory response induced by LPS, thereby preventing periodontal inflammation and reducing the development of peri-implantitis.

scholarly journals Daphnetin inhibits proliferation and inflammatory response in human HaCaT keratinocytes and ameliorates imiquimod-induced psoriasis-like skin lesion in mice

2020 ◽  
Vol 53 (1) ◽  
Author(s):  
Jintao Gao ◽  
Fangru Chen ◽  
Huanan Fang ◽  
Jing Mi ◽  
Qi Qi ◽  
...  
Keyword(s):  
Skin Lesion ◽  
Inflammatory Response ◽  
Mouse Model ◽  
Nuclear Translocation ◽  
Marker Gene ◽  
Inflammatory Factors ◽  
Mrna Levels ◽  
Hacat Keratinocytes ◽  
Tnf Α

Abstract Background Psoriasis is a common chronic inflammatory skin disease. Keratinocytes hyperproliferation and excessive inflammatory response contribute to psoriasis pathogenesis. The agents able to attenuate keratinocytes hyperproliferation and excessive inflammatory response are considered to be potentially useful for psoriasis treatment. Daphnetin exhibits broad bioactivities including anti-proliferation and anti-inflammatory. This study aims to evaluate the anti-psoriatic potential of daphnetin in vitro and in vivo, and explore underlying mechanisms. Methods HaCaT keratinocytes was stimulated with the mixture of IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5) to establish psoriatic keratinocyte model in vitro. Cell viability was measured using Cell Counting Kit-8 (CCK-8). Quantitative Real-Time PCR (qRT-PCR) was performed to measure the mRNA levels of hyperproliferative marker gene keratin 6 (KRT6), differentiation marker gene keratin 1 (KRT1) and inflammatory factors IL-1β, IL-6, IL-8, TNF-α, IL-23A and MCP-1. Western blotting was used to detect the protein levels of p65 and p-p65. Indirect immunofluorescence assay (IFA) was carried out to detect p65 nuclear translocation. Imiquimod (IMQ) was used to construct psoriasis-like mouse model. Psoriasis severity (erythema, scaling) was scored based on Psoriasis Area Severity Index (PASI). Hematoxylin and eosin (H&E) staining was performed to examine histological change in skin lesion. The expression of inflammatory factors including IL-6, TNF-α, IL-23A and IL-17A in skin lesion was measured by qRT-PCR. Results Daphnetin attenuated M5-induced hyperproliferation in HaCaT keratinocytes. M5 stimulation significantly upregulated mRNA levels of IL-1β, IL-6, IL-8, TNF-α, IL-23A and MCP-1. However, daphnetin treatment partially attenuated the upregulation of those inflammatory cytokines. Daphnetin was found to be able to inhibit p65 phosphorylation and nuclear translocation in HaCaT keratinocytes. In addition, daphnetin significantly ameliorate the severity of skin lesion (erythema, scaling and epidermal thickness, inflammatory cell infiltration) in IMQ-induced psoriasis-like mouse model. Daphnetin treatment attenuated IMQ-induced upregulation of inflammatory cytokines including IL-6, IL-23A and IL-17A in skin lesion of mice. Conclusions Daphnetin was able to attenuate proliferation and inflammatory response induced by M5 in HaCaT keratinocytes through suppression of NF-κB signaling pathway. Daphnetin could ameliorate the severity of skin lesion and improve inflammation status in IMQ-induced psoriasis-like mouse model. Daphnetin could be an attractive candidate for future development as an anti-psoriatic agent.

Effects of Metformin on Life Span, Cognitive Ability, and Inflammatory Response in a Short-Lived Fish

2020 ◽  
Vol 75 (11) ◽  
pp. 2042-2050 ◽  
Author(s):  
Juntong Wei ◽  
He Qi ◽  
Keke Liu ◽  
Changsheng Zhao ◽  
Yan Bian ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Life Span ◽  
Cognitive Ability ◽  
Healthy Aging ◽  
Natural Aging ◽  
Serum Levels ◽  
Annual Fish ◽  
Tnf Α ◽  
Accelerated Growth ◽  
Nothobranchius Guentheri

Abstract Metformin, an oral antidiabetic drug, prolongs the life span in nematode, silkworm, and other transgenic rodents, but its effects on longevity and aging-related cognitive ability using natural aging vertebrate models remain poorly understood. The genus of annual fish Nothobranchius show accelerated growth and expression of aging biomarkers. Here, using the short-lived fish Nothobranchius guentheri, we investigated effects of metformin on life span and aging-related cognitive ability and inflammation. Total of 145 fish, 72 fish were fed with metformin in the concentration of 2 mg/g food and 73 fish without metformin from 16 weeks of age until the end of their lives. The chronic feeding with metformin prolonged the life span of the fish and delayed aging with retarded accumulation of lipofuscin in liver, senescence-associated beta-galactosidase (SA-β-gal) activity in skin and serum levels of cholesterol and triglyceride significantly in the 10-month-old fish. Furthermore, metformin improved motor, learning, and memory skills by behavior tests accompanying with reduction of SA-β-gal activity and neurofibrillary degeneration and inhibition of inflammatory response including downregulated NF-κB and proinflammatory cytokines IL-8, TNF-α, and IL-1β expression and enhanced anti-inflammatory cytokine IL-10 level in brain. These findings demonstrate that metformin prolongs the life span and exerts neuroprotective and anti-inflammation function to improve cognitive ability in annual fish. It might be an effective strategy by using metformin to raise the possibility of promoting healthy aging of old population in aging process.

scholarly journals The Macrophage Scavenger Receptor Type A Is Expressed by Activated Macrophages and Protects the Host Against Lethal Endotoxic Shock

1997 ◽  
Vol 186 (9) ◽  
pp. 1431-1439 ◽  
Author(s):  
Richard Haworth ◽  
Nick Platt ◽  
Satish Keshav ◽  
Derralynn Hughes ◽  
Elisabeth Darley ◽  
...  
Keyword(s):  
Host Defense ◽  
Bacterial Infections ◽  
Endotoxic Shock ◽  
Scavenger Receptor ◽  
Type A ◽  
Lipoteichoic Acid ◽  
Protective Role ◽  
Infection Model ◽  
Macrophage Scavenger Receptor ◽  
Tnf Α

During gram-negative bacterial infections, lipopolysaccharide (LPS) stimulates primed macrophages (Mφ) to release inflammatory mediators such as tumor necrosis factor (TNF)-α, which can cause hypotension, organ failure, and often death. Several different receptors on Mφ have been shown to bind LPS, including the type A scavenger receptor (SR-A). This receptor is able to bind a broad range of polyanionic ligands such as modified lipoproteins and lipoteichoic acid of gram-positive bacteria, which suggests that SR-A plays a role in host defense. In this study, we used mice lacking the SR-A (SRKO) to investigate the role of SR-A in acquired immunity using a viable bacillus Calmette Guérin (BCG) infection model. We show that activated Mφ express SR-A and that this molecule is functional in assays of adhesion and endocytic uptake. After BCG infection, SRKO mice are able to recruit Mφ to sites of granuloma formation where they become activated and restrict BCG replication. However, infected mice lacking the SR-A are more susceptible to endotoxic shock and produce more TNF-α and interleukin-6 in response to LPS. In addition, we show that an antibody which blocks TNF-α activity reduces LPS-induced mortality in these mice. Thus SR-A, expressed by activated Mφ, plays a protective role in host defense by scavenging LPS as well as by reducing the release by activated Mφ of proinflammatory cytokines. Modulation of SR-A may provide a novel therapeutic approach to control endotoxic shock.

scholarly journals Inflammatory and immunogenetic markers in correlation with pulmonary tuberculosis

2013 ◽  
Vol 39 (6) ◽  
pp. 719-727 ◽  
Author(s):  
Beatriz Lima Alezio Muller ◽  
Daniela Maria de Paula Ramalho ◽  
Paula Fernanda Gonçalves dos Santos ◽  
Eliene Denites Duarte Mesquita ◽  
Afranio Lineu Kritski ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Pulmonary Tuberculosis ◽  
Gene Polymorphisms ◽  
Serum Levels ◽  
Acute Inflammatory Response ◽  
Reactive Protein ◽  
Antituberculosis Treatment ◽  
Tnf Α ◽  
Referral Hospitals ◽  
Ifn Γ

OBJECTIVE: To describe serum levels of the cytokines IL-10, TNF-α, and IFN-γ, as well as polymorphisms in the genes involved in their transcription, and their association with markers of the acute inflammatory response in patients with pulmonary tuberculosis.METHODS: This was a descriptive, longitudinal study involving 81 patients with pulmonary tuberculosis treated at two referral hospitals. We collected data on sociodemographic variables and evaluated bacteriological conversion at the eighth week of antituberculosis treatment, gene polymorphisms related to the cytokines studied, and serum levels of those cytokines, as well as those of C-reactive protein (CRP). We also determined the ESR and CD4+ counts.RESULTS: The median age of the patients was 43 years; 67 patients (82.7%) were male; and 8 patients (9.9%) were infected with HIV. The ESR was highest in the patients with high IFN-γ levels and low IL-10 levels. IFN-γ and TNF-α gene polymorphisms at positions +874 and −238, respectively, showed no correlations with the corresponding cytokine serum levels. Low IL-10 levels were associated with IL-10 gene polymorphisms at positions −592 and −819 (but not −1082). There was a negative association between bacteriological conversion at the eighth week of treatment and CRP levels.CONCLUSIONS: Our results suggest that genetic markers and markers of acute inflammatory response are useful in predicting the response to antituberculosis treatment.

Soluble levels and endogenous vascular gene expression of KLOTHO are related to inflammation in human atherosclerotic disease

2017 ◽  
Vol 131 (21) ◽  
pp. 2601-2609 ◽  
Author(s):  
Ernesto Martín-Núñez ◽  
Javier Donate-Correa ◽  
Ángel López-Castillo ◽  
Alejandro Delgado-Molinos ◽  
Carla Ferri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Serum Levels ◽  
Atherosclerotic Disease ◽  
Inflammatory Disorder ◽  
Mrna Levels ◽  
Atherosclerotic Vascular Disease ◽  
Chronic Inflammatory Disorder ◽  
Control Subjects ◽  
Inflammatory Status ◽  
Tnf Α

Atherosclerosis is a chronic inflammatory disorder affecting the artery wall. Klotho, an anti-aging factor expressed in the vessel walls that participates in the maintenance of vascular homeostasis, can be down-regulated by inflammation. In this proof-of-concept work we seek to characterize the arterial KLOTHO expression in the vascular wall, as well as the serum concentration of this protein, in a group of patients with clinical atherosclerotic disease. In addition, we aim to analyze the relationship between Klotho and inflammation. Vascular samples were obtained from 27 patients with atherosclerotic disease under an elective vascular surgery procedure, and from 11 control subjects (cadaveric organ donation programme). qRT-PCR was performed to analyze the gene expression of KLOTHO, TNF-α, IL-6, and IL-10. Serum levels of soluble KLOTHO were measured by ELISA. As compared with control subjects, serum concentrations and vascular expression of Klotho were lower in patients with atherosclerotic vascular disease, whereas inflammatory status was significantly higher. There was a negative and significant correlation between inflammatory parameters and Klotho. After controlling for the effect of other variables, partial correlation showed a direct relationship between vascular KLOTHO gene expression and IL-10 mRNA levels, whereas there was a negative association with serum LDL concentrations and vascular TNF-α expression. Our study indicates an inverse interrelationship between inflammation and Klotho in atherosclerosis. Further studies are necessary to elucidate whether the inflammatory state causes Klotho deficiency or, on the contrary, reduction of Klotho could be responsible for greater inflammation, and finally, to investigate the potential clinical relevance of this association.

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