scholarly journals Diesel Exhaust Particulates Induce Neutrophilic Lung Inflammation by Modulating Endoplasmic Reticulum Stress-Mediated CXCL1/KC Expression in Alveolar Macrophages

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 6046 ◽  
Author(s):  
Dong Im Kim ◽  
Mi-Kyung Song ◽  
Hye-In Kim ◽  
Kang Min Han ◽  
Kyuhong Lee
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Alveolar Macrophages ◽  
Diesel Exhaust ◽  
Lung Inflammation ◽  
Binding Protein ◽  
In Vitro Study ◽  
Vitro Study

Diesel exhaust particulates (DEP) have adverse effects on the respiratory system. Endoplasmic reticulum (ER) abnormalities contribute to lung inflammation. However, the relationship between DEP exposure and ER stress in the respiratory immune system and especially the alveolar macrophages (AM) is poorly understood. Here, we examined ER stress and inflammatory responses using both in vivo and in vitro study. For in vivo study, mice were intratracheally instilled with 25, 50, and 100 μg DEP and in vitro AM were stimulated with DEP at 1, 2, and 3 mg/mL. DEP increased lung weight and the number of inflammatory cells, especially neutrophils, and inflammatory cytokines in bronchoalveolar lavage fluid of mice. DEP also increased the number of DEP-pigmented AM and ER stress markers including bound immunoglobulin protein (BiP) and CCAAT/enhancer binding protein-homologous protein (CHOP) were upregulated in the lungs of DEP-treated mice. In an in vitro study, DEP caused cell damage, increased intracellular reactive oxygen species, and upregulated inflammatory genes and ER stress-related BiP, CHOP, splicing X-box binding protein 1, and activating transcription factor 4 expressions in AM. Furthermore, DEP released the C-X-C Motif Chemokine Ligand 1 (CXCL1/KC) in AM. In conclusion, DEP may contribute to neutrophilic lung inflammation pathogenesis by modulating ER stress-mediated CXCL1/KC expression in AM.

scholarly journals Diesel exhaust particulates induce neutrophilic lung inflammation by modulating endoplasmic reticulum stress-mediated CXCL1/KC expression in alveolar macrophages

2020 ◽  
Author(s):  
Dong Im Kim ◽  
Mi-Kyung Song ◽  
Kyuhong Lee
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Alveolar Macrophages ◽  
Diesel Exhaust ◽  
Lung Inflammation ◽  
Inflammatory Responses ◽  
Cell Damage ◽  
Interferon Γ ◽  
Mouse Lung ◽  
Lung Weight

Abstract Background Exposure to particular matter (PM)2.5, including diesel exhaust particulates (DEP), has adverse effects on the respiratory system. Endoplasmic reticulum (ER) abnormalities contribute to respiratory disease pathogenesis such as lung inflammation. However, there is little published research on the relationship between DEP exposure and ER stress in the respiratory immune system and especially the alveolar macrophages (AM). Here, we examined ER stress and inflammatory responses in a DEP-induced murine lung inflammation model and in DEP-stimulated AM.Results DEP treatment increased relative lung weight and the number of total cells, neutrophils, and lymphocytes in mouse BALF. Histological examinations also showed that DEP exposure induced neutrophilic lung inflammation and increased the number of DEP-pigmented AM. Western blot analysis showed that BiP and CHOP were relatively upregulated in DEP-induced mouse lung tissues. DEP caused cell damage, increased intracellular reactive oxygen species (ROS), and upregulated the genes associated with inflammation (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, interferon-γ, and toll-like receptor 4) and with ER stress (bound immunoglobulin protein [BiP], CCAAT/enhancer binding protein-homologous protein [CHOP], sXBP-1, and activating transcription factor 4) in AM. Furthermore, DEP stimulation upregulated the gene encoding the chemokine CXCL1/KC in AM.Conclusions DEP may contribute to neutrophilic lung inflammation pathogenesis by modulating ER stress-mediated CXCL1/KC expression in alveolar macrophages.

p-Coumaric Acid Attenuates Lipopolysaccharide-Induced Lung Inflammation in Rats by Scavenging ROS Production: an In Vivo and In Vitro Study

Inflammation ◽  
2019 ◽  
Vol 42 (6) ◽  
pp. 1939-1950 ◽  
Author(s):  
Maryam Kheiry ◽  
Mahin Dianat ◽  
Mohammad Badavi ◽  
Seyyed Ali Mard ◽  
Vahid Bayati
Keyword(s):  
Lung Inflammation ◽  
In Vitro Study ◽  
Vitro Study ◽  
Ros Production ◽  
Coumaric Acid

scholarly journals Protection of pancreatic β-cells by exendin-4 may involve the reduction of endoplasmic reticulum stress; in vivo and in vitro studies

2007 ◽  
Vol 193 (1) ◽  
pp. 65-74 ◽  
Author(s):  
Shin Tsunekawa ◽  
Naoki Yamamoto ◽  
Katsura Tsukamoto ◽  
Yuji Itoh ◽  
Yukiko Kaneko ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Islet Cells ◽  
Binding Protein ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells

The aim of this study was to investigate the in vivo and in vitro effects of exendin-4, a potent glucagon-like peptide 1 agonist, on the protection of the pancreatic β-cells against their cell death. In in vivo experiments, we used β-cell-specific calmodulin-overexpressing mice where massive apoptosis takes place in their β-cells, and we examined the effects of chronic treatment with exendin-4. Chronic and s.c. administration of exendin-4 reduced hyperglycemia. The treatment caused significant increases of the insulin contents of the pancreas and islets, and retained the insulin-positive area. Dispersed transgenic islet cells lived only shortly, and several endoplasmic reticulum (ER) stress-related molecules such as immunoglobulin-binding protein (Bip), inositol-requiring enzyme-1α, X-box-binding protein-1 (XBP-1), RNA-activated protein kinase-like endoplasmic reticulum kinase, activating transcription factor-4, and C/EBP-homologous protein (CHOP) were more expressed in the transgenic islets. We also found that the spliced form of XBP-1, a marker of ER stress, was also increased in β-cell-specific calmodulin-overexpressing transgenic islets. In the quantitative real-time PCR analyses, the expression levels of Bip and CHOP were reduced in the islets from the transgenic mice treated with exendin-4. These findings suggest that excess of ER stress occurs in the transgenic β-cells, and the suppression of ER stress and resultant protection against cell death may be involved in the anti-diabetic effects of exendin-4.

scholarly journals The Cardiotoxicity Induced by Arsenic Trioxide is Alleviated by Salvianolic Acid A via Maintaining Calcium Homeostasis and Inhibiting Endoplasmic Reticulum Stress

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 543 ◽  
Author(s):  
Ruiying Wang ◽  
Jingyi Zhang ◽  
Shan Wang ◽  
Min Wang ◽  
Tianyuan Ye ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Arsenic Trioxide ◽  
Calcium Homeostasis ◽  
In Vitro Study ◽  
Protective Effects ◽  
Salvianolic Acid ◽  
Salvianolic Acid A

Arsenic trioxide (ATO) has been verified as a breakthrough with respect to the management of acute promyelocytic leukemia (APL) in recent decades but associated with some serious adverse phenomena, particularly cardiac functional abnormalities. Salvianolic acid A (Sal A) is a major effective component in treating ATO-induced cardiotoxicity. Therefore, the objective of our study was to assess whether Sal A had protective effects by the regulation of calcium homeostasis and endoplasmic reticulum (ER) stress. For the in vivo study, BALB/c mice were treated with ATO and/or Sal A via daily tail vein injections for two weeks. For the in vitro study, we detected the effects of ATO and/or Sal A in real time using adult rat ventricular myocytes (ARVMs) and an IonOptix MyoCam system. Our results showed that Sal A pretreatment alleviated cardiac dysfunction and Ca2+ overload induced by ATO in vivo and vitro. Moreover, Sal A increased sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA) activity and expression, alleviated [Ca2+]ER depletion, and decreased ER stress-related protein expression. Sal A protects the heart from ATO-induced injury and its administration correlates with the modulation of SERCA, the recovery of Ca2+ homeostasis, and the down-regulation of ER stress-mediated apoptosis.

Effects of TSH and calcitriol on bone metabolism: in vivo and in vitro study

2014 ◽  
Author(s):  
Ivo Dumic-Cule ◽  
Dunja Rogic ◽  
Damir Jezek ◽  
Lovorka Grgurevic ◽  
Slobodan Vukicevic
Keyword(s):  
Bone Metabolism ◽  
In Vitro Study ◽  
Vitro Study

scholarly journals Dehydrodiisoeugenol inhibits colorectal cancer growth by endoplasmic reticulum stress-induced autophagic pathways

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Changhong Li ◽  
Kui Zhang ◽  
Guangzhao Pan ◽  
Haoyan Ji ◽  
Chongyang Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Endoplasmic Reticulum ◽  
Cell Growth ◽  
Er Stress ◽  
Cancer Cells ◽  
Tumor Xenograft ◽  
Anticancer Activities ◽  
Colorectal Cancer Cells

Abstract Background Dehydrodiisoeugenol (DEH), a novel lignan component extracted from nutmeg, which is the seed of Myristica fragrans Houtt, displays noticeable anti-inflammatory and anti-allergic effects in digestive system diseases. However, the mechanism of its anticancer activity in gastrointestinal cancer remains to be investigated. Methods In this study, the anticancer effect of DEH on human colorectal cancer and its underlying mechanism were evaluated. Assays including MTT, EdU, Plate clone formation, Soft agar, Flow cytometry, Electron microscopy, Immunofluorescence and Western blotting were used in vitro. The CDX and PDX tumor xenograft models were used in vivo. Results Our findings indicated that treatment with DEH arrested the cell cycle of colorectal cancer cells at the G1/S phase, leading to significant inhibition in cell growth. Moreover, DEH induced strong cellular autophagy, which could be inhibited through autophagic inhibitors, with a rction in the DEH-induced inhibition of cell growth in colorectal cancer cells. Further analysis indicated that DEH also induced endoplasmic reticulum (ER) stress and subsequently stimulated autophagy through the activation of PERK/eIF2α and IRE1α/XBP-1 s/CHOP pathways. Knockdown of PERK or IRE1α significantly decreased DEH-induced autophagy and retrieved cell viability in cells treated with DEH. Furthermore, DEH also exhibited significant anticancer activities in the CDX- and PDX-models. Conclusions Collectively, our studies strongly suggest that DEH might be a potential anticancer agent against colorectal cancer by activating ER stress-induced inhibition of autophagy.

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