Focal localization of inflammatory cytokines and neurotrophins in a tongue chronic injury model

Background: Sepsis often leads to systemic multiple organ dysfunction, with the majority of deaths attributable to acute myocardial injury (AMI). In this study, we aimed to explore the functional role of miR-365a-3p in sepsis induced AMI. Materials and methods: The sepsis myocardial injury model was constructed using lipopolysaccharide (LPS) both in vitro and in vivo with selective regulation of miR-365a-3p expression. RT-PCR or western blot was employed to detect the expressions of miR-365a-3p, inflammatory cytokines (TNF-α, IL6, IL-1β), and inflammation-related proteins (NF-κB, I-κB, MyD88) in myocardial tissues and cells. Also, cell counting kit-8 (CCK8) and flow cytometry assays were used measuring cardiomyocyte proliferation and apoptosis, respectively. Furthermore, the targeting relationship between miR-365a-3p and MyD88 was verified with the dual luciferase activity assay. Results: MiR-365a-3p was down-regulated in LPS-induced myocardial injury model. MiR-365a-3p overexpression attenuated cardiomyocyte apoptosis, and suppressed the expressions of inflammatory cytokines and proteins. Inhibiting miR-365a-3p, however, produced the opposite effects. Mechanistically, miR-365a-3p targeted the 3'-untranslated region (3’UTR) of MyD88, thereby inactivating MyD88 mediated NF-κB pathway. Conclusion: MiR-365a-3p overexpression mitigated sepsis-mediated myocardial injury by inhibiting MyD88-mediated NF-κB activation.

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LncRNA PFAL suppresses TNF-α-induced inflammation by upregulating miR-18a in WI-38 cells

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i12.5 ◽

2021 ◽

Vol 19 (12) ◽

pp. 2513-2520

Author(s):

Yichun Xie ◽

Hongqun Wang

Keyword(s):

Cell Viability ◽

Inflammatory Cytokines ◽

Cell Apoptosis ◽

Cell Injury ◽

Inflammatory Diseases ◽

Jnk Pathway ◽

Inflammatory Injury ◽

Mortality And Morbidity ◽

Injury Model ◽

Tnf Α

Purpose: Pneumonia is a serious respiratory disease among children with high mortality and morbidity all over the world. Long non-coding RNAs have been proven to play a vital role in many inflammatory diseases including pneumonia. In the present study, the protective impact of lncRNA PFAL on cell viability, cell apoptosis and secretion of inflammatory cytokines, as well as the underlying molecular mechanism in TNF-α-induced inflammatory injury model of pneumonia were investigated.Methods: WI-38 cell line was treated with 20 ng/ml TNF-α to establish an inflammatory injury model of pneumonia. LncRNA PFAL or miR-18a was up- or down-regulated in the WI-38 cells by transfection procedure. Cell viability was assessed using CCK-8 assay, while the rate of cell apoptosis was measured by utilizing flow cytometry. The mRNA expression levels of lncRNA PFAL, miR-18a, apoptosis-related and JNK pathway genes were determined with RT-qPCR. Moreover, the production of inflammatory cytokines such as IL-6 and MCP-1 were detected by using Western blot analysis.Results: The results indicated that cell viability was significantly (P<0.05) reduced, while the rate of cell apoptosis was increased in the TNF-α-induced WI-38 cells. Also, TNF-α treatment enhanced the expression of inflammatory cytokines that included IL-6 and MCP-1 in WI-38 cells. Overexpression of PFAL suppressed the injury induced by TNF-α and miR-18a was positively regulated by PFAL. Moreover, the inhibition of miR-18a weakens the effect of PFAL overexpression in TNF-α-induced cell injury. Furthermore, PFAL and miR-18a were involved in the regulation of JNK pathway.Conclusion: Overexpression of PFAL suppresses TNF-α-induced WI-38 cell injury by up-regulating miR-18a via the inactivation of JNK signaling pathway. Keywords: Inflammation, JNK pathway, miR-18a, PFAL, Pneumonia, TNF-α

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374 Bves Contributes to Colonic Wound Healing in a Chronic Injury Model

Gastroenterology ◽

10.1016/s0016-5085(16)30399-7 ◽

2016 ◽

Vol 150 (4) ◽

pp. S84

Author(s):

Yash A. Choksi ◽

Cody Keating ◽

Sarah P. Short ◽

Patricia Costacurta ◽

Kan He ◽

...

Keyword(s):

Wound Healing ◽

Chronic Injury ◽

Injury Model ◽

Colonic Wound

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FTY720 Attenuates Angiotensin II-Induced Podocyte Damage via Inhibiting Inflammatory Cytokines

Mediators of Inflammation ◽

10.1155/2017/3701385 ◽

2017 ◽

Vol 2017 ◽

pp. 1-14 ◽

Cited By ~ 9

Author(s):

Ke Su ◽

Ping Zeng ◽

Wei Liang ◽

Zhengyu Luo ◽

Yiman Wang ◽

...

Keyword(s):

Iga Nephropathy ◽

Inflammatory Cytokines ◽

Renal Injury ◽

Chemical Substance ◽

Ang Ii ◽

Potential Mechanism ◽

Podocyte Injury ◽

Podocyte Damage ◽

Injury Model ◽

Sphingosine 1 Phosphate

FTY720, a new chemical substance derived from the ascomyceteIsaria sinclairii, is used for treating multiple sclerosis, renal cancer, and asthma. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid metabolite and exists in red blood cells. FTY720 is a synthetic S1P analog which can block S1P evoking physiological effects. Recently studies show that S1P was participating in activated inflammation cells induced renal injury. The objective of this study was to assess the protective effect of FTY720 on kidney damage and the potential mechanism of FTY720 which alleviate podocyte injury in chronic kidney disease. In this study, we selected 40 patients with IgA nephropathy and examined their clinical characteristics. Ang II-infusion rat renal injury model was established to evaluate the glomeruli and tubulointerstitial lesion. The result showed that the concentration of S1P in serum and urine was positively correlated with IgA nephropathy patients’ renal injury. FTY720 could reduce renal histological lesions induced by Ang II-infusion in rats. Moreover, FTY720 decreased S1P synthesis in Ang II-infusion rats via downregulation of inflammatory cytokines including TNF-αand IL-6. In addition, FTY720 alleviated exogenous S1P-induced podocyte damage. In conclusion, FTY720 is able to attenuate S1P-induced podocyte damage via reducing inflammatory cytokines.

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Abstract 1318: Aging Inhibits The Apoptotic Resolution Of Inflammation Leading To An Exaggerated Neointimal Development In Response To Vascular Injury.

Circulation ◽

10.1161/circ.116.suppl_16.ii_270 ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Roberto I Vazquez-Padron ◽

Yuntao Wei ◽

Dania Mateo ◽

Sen Li ◽

Sashi Salgar ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Vascular Injury ◽

Apoptotic Cells ◽

Balloon Injury ◽

Neointimal Formation ◽

Injury Model ◽

Inflammatory Phenotype ◽

The Media ◽

Inflammatory Response To Injury ◽

Alpha Actin

Objective : This study aims to determine the mechanisms by which aging prolongs inflammation in response to vascular injury, and exaggerate neointimal formation. Methods and Results : Using balloon injury model in rat iliac arteries, we found that aging rats (22 month-old) developed thicker neointima at 4 weeks after injury than their younger counter parts (4 month-old) (I/M: 0.8 ± 0.2 vs. 0.54 ± 0.15, p<0.008). We also found that injured arteries in aging animals accumulated more alpha-actin positive VSMC in the neointima than those from the young ones (500 ± 100 vs. 320 ± 120 cell/mm 2 ). Although similar number of macrophages (CD68+; detected by immunohistochemistry; IHC) appeared in the adventitia 24 h after injury in both groups, these cells disappeared in the young arteries after 3 days, while remained in the media and neointima of aging arteries until 30 days after injury. Macrophages in aging arteries were CD163 negative and IL-6 and IL-18 positive, indicating they are of pro-inflammatory phenotype. There were no differences in the number of vascular T cells and dendritic cells between groups. Vascular apoptotic cells were determined by ISOL combined with IHC either for VSMC or macrophages. Aging arteries had fewer apoptotic VSMC or macrophages (0.2% ± 0.05) at any time after vascular injury when compared with the younger ones which had abundant vascular apoptotic cells in the media and neointima at 7 days after surgery (2.7% ± 0.45). Finally, the vascular cytokines production was assessed after balloon injury using the LincoPlex system. At three days after injury aging arteries contained three folds or higher levels of IL18, IL-6, Gro KC, and Leptin than the young ones. These pro-inflammatory cytokines stayed elevated in the aging vessels for most of the arterial remodeling process. In contrast, when compared with aging arteries, young arteries produced three times or higher levels of anti-inflammatory cytokines IL-10, IL-17, IL13 and IL-9 at seven days after injury. Conclusions : Our data suggests that aging inhibits the apoptotic resolution of the vascular inflammatory response to injury, leading to exaggerated neointimal formation.

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Correlation between leptin and pro-inflammatory cytokines in cortical contusion injury model

Turkish Journal of Trauma and Emergency Surgery ◽

10.5505/tjtes.2011.69077 ◽

2011 ◽

Vol 17 (4) ◽

pp. 298-302 ◽

Cited By ~ 1

Author(s):

Alper Karaoglan ◽

Osman Akdemir ◽

Nilgun Cinar ◽

Mehmet Alpay Cal ◽

Bilal Kelten ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Injury Model ◽

Contusion Injury ◽

Cortical Contusion ◽

Pro Inflammatory Cytokines

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Dexmedetomidine Protects Against Septic Liver Injury by Enhancing Autophagy Through Activation of the AMPK/SIRT1 Signaling Pathway

Frontiers in Pharmacology ◽

10.3389/fphar.2021.658677 ◽

2021 ◽

Vol 12 ◽

Author(s):

Qing Yu ◽

Liying Zou ◽

Xiu Yuan ◽

Fang Fang ◽

Feng Xu

Keyword(s):

Liver Injury ◽

Western Blotting ◽

Inflammatory Cytokines ◽

Inflammatory Responses ◽

Early Stage ◽

Morphological Changes ◽

Cecal Ligation ◽

Injury Model ◽

Associated Proteins

Background: Liver injury is one of the serious complications of sepsis. Previous studies suggested that dexmedetomidine (DEX) could alleviate cecal ligation and puncture (CLP)-induced liver injury. However, it is unclear whether the protective effect of DEX on sepsis-induced liver injury is related to autophagy.Methods: Mice (n = 105) were randomly divided into the following groups: (i) CON group (Sham); (ii) CLP group (CLP-induced liver injury + saline); (iii) CLP + DEX group (CLP-induced liver injury + DEX). Mouse models of sepsis-induced liver injury were established using CLP. DEX or normal saline was administered by intraperitoneal injection at 0, 2, and 4 h after CLP surgery. The mortality rate within 120 h was calculated. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and inflammatory cytokines were measured at 6, 12, and 24 h in each group. Hematoxylin and eosin staining assay was carried out to detect the morphological changes of mouse liver cells in each group. The levels of autophagy-associated proteins LC3II, Beclin-1, p62, and LAMP-2 were detected in three groups of mice using western blotting. The expression of LC3II was detected using immunofluorescence. Transmission electron microscopy (TEM) of liver tissue was used to observe autophagosomes and autophagosome–lysosomes. Lastly, the effect of DEX on the AMPK/SIRT1 pathway-associated protein levels were detected using western blotting. Meanwhile, we used L0-2 cells infected with mRFP-GFP-LC3 adenovirus to further analyze the role of SIRT1 in DEX-induced autophagy in liver injury model in vitro.Results: DEX significantly improved the survival rate of septic mice at the early stage and ameliorated the pathology of sepsis-induced liver injury. The level of autophagy-associated proteins, phosphorylated (p)-AMPK/AMPK, and SIRT1 in the liver of CLP-induced sepsis mice peaked at 12 h post-CLP and decreased significantly at 24 h. In the CLP + DEX group, the levels of autophagy-associated proteins, p-AMPK/AMPK, and SIRT1 increased, whereas inflammatory cytokines decreased at 24 h. The autophagosome structure was clearly observed at different time points in the CLP + DEX group. In the in vitro hepatocyte injury model, the SIRT1 inhibitor significantly increased intracellular ROS levels and reversed the effect of DEX on autophagy flux.Conclusion: We demonstrated a novel mechanism in which DEX protects against CLP-induced liver injury. DEX enhances autophagy, which alleviates the inflammatory responses in CLP-induced liver injury by regulating the SIRT1/AMPK pathway.

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Human engineered heart tissue transplantation in a guinea pig chronic injury model

10.1101/2021.06.28.450176 ◽

2021 ◽

Author(s):

Constantin von Bibra ◽

Aya Shibamiya ◽

Birgit Geertz ◽

Eva Querdel ◽

Maria Koehne ◽

...

Keyword(s):

Guinea Pig ◽

Myocardial Injury ◽

Heart Tissue ◽

Left Ventricular ◽

Positive Staining ◽

Chronic Injury ◽

Engineered Heart Tissue ◽

Injury Model ◽

Significant Difference ◽

Regenerative Approach

Myocardial injury leads to an irreversible loss of cardiomyocytes (CM). The implantation of human engineered heart tissue (EHT) has become a promising regenerative approach. Previous studies exhibited beneficial, dose-dependent effects of human induced pluripotent stem cell (hiPSC)-derived EHT patch transplantation in a guinea pig model in the subacute phase of myocardial injury. Yet, advanced heart failure often results from a chronic remodeling process. Therefore, from a clinical standpoint it is worthwhile to explore the ability to repair the chronically injured heart. In this study human EHT patches were generated from hiPSC-derived CM (15x10^6 cells) and implanted epicardially four weeks after injury in a guinea-pig cryo-injury model. Cardiac function was evaluated by echocardiography after a follow-up period of four weeks. Hearts revealed large transmural myocardial injuries amounting to 27% of the left ventricle. EHT recipient hearts demonstrated compact muscle islands of human origin in the scar region, as indicated by a positive staining for human Ku80 and dystrophin, remuscularizing 5% of the scar area. Echocardiographic analysis demonstrated no significant difference between animals that received EHT patches and animals in the control group. Thus, EHT patches engrafted in the chronically injured heart but in contrast to the subacute model, grafts were smaller and EHT patch transplantation did not improve left ventricular function, highlighting the difficulties for a regenerative approach.

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Cytokine synergy, collagenases and cartilage collagen breakdown

Biochemical Society Symposium ◽

10.1042/bss0700125 ◽

2003 ◽

Vol 70 ◽

pp. 125-133 ◽

Cited By ~ 7

Author(s):

Tim E. Cawston ◽

Jenny M. Milner ◽

Jon B. Catterall ◽

Andrew D. Rowan

Keyword(s):

Matrix Metalloproteinases ◽

Inflammatory Cytokines ◽

Activator Protein 1 ◽

Activator Protein ◽

And Cartilage ◽

Pro Inflammatory Cytokines

We have investigated proteinases that degrade cartilage collagen. We show that pro-inflammatory cytokines act synergistically with oncastatin M to promote cartilage collagen resorption by the up-regulation and activation of matrix metalloproteinases (MMPs). The precise mechanisms are not known, but involve the up-regulation of c-fos, which binds to MMP promoters at a proximal activator protein-1 (AP-1) site. This markedly up-regulates transcription and leads to higher levels of active MMP proteins.

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