scholarly journals GPR84 inhibitor ameliorated lung inflammation and modulated NF-κB through MAPK signalling pathway

2021 ◽  
Author(s):  
Ting Wang ◽  
Yan Zou ◽  
He Lv
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Inflammation ◽  
Cell Model ◽  
Signalling Pathway ◽  
Tunel Staining ◽  
Mapk Signalling Pathway ◽  
Mapk Signalling ◽  
Lps Treatment

Abstract We set our experiments to investigate the role of GPR84 in LPS-induced acute lung injury. The expression of GPR84 was detected through RT-qPCR and Western blotting (WB) after LPS treatment in ALI mouse and cell model, respectively. Following the treatment of GPR 84 inhibitor, the lung injury was evaluated through HE staining while the MAPK signalling components were analyzed through WB, as well as NF-κB signalling components. These components were further analyzed by the addition of anisomycin or TPA. The analysis of apoptosis was performed through TUNEL staining. We showed that LPS stimulated the expression of GPR84 expression. GPR 84 inhibitor facilitated the activation of MAPK signalling while inhibiting MAPK signalling, these effects of which were further rescued by anisomycin or TPA treatment. In conclusion, our findings support that GPR84 inhibitor improved lung injury caused by LPS and revealed a role of GPR87 modulating NF-κB through MAPK signalling pathway. Altogether, GPR84 could be as a prospective target for the treatment of ALI.

scholarly journals Mitochondrial peptides cause proinflammatory responses in the alveolar epithelium via FPR-1, MAPKs, and AKT: a potential mechanism involved in acute lung injury

2018 ◽  
Vol 315 (5) ◽  
pp. L775-L786 ◽  
Author(s):  
Xue Zhang ◽  
Tao Wang ◽  
Zhi-Cheng Yuan ◽  
Lu-Qi Dai ◽  
Ni Zeng ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Inflammation ◽  
Cell Injury ◽  
Specific Inhibitor ◽  
Alveolar Epithelium ◽  
Formyl Peptide Receptor ◽  
Potential Mechanism ◽  
Alveolar Epithelial

Acute lung injury (ALI) is characterized by alveolar epithelial damage and uncontrolled pulmonary inflammation. Mitochondrial damage-associated molecular patterns (DAMPs), including mitochondrial peptides [ N-formyl peptides (NFPs)], are released during cell injury and death and induce inflammation by unclear mechanisms. In this study, we have investigated the role of mitochondrial DAMPs (MTDs), especially NFPs, in alveolar epithelial injury and lung inflammation. In murine models of ALI, high levels of mitochondrial NADH dehydrogenase 1 in bronchoalveolar lavage fluid (BALF) were associated with lung injury scores and increased formyl peptide receptor (FPR)-1 expression in the alveolar epithelium. Cyclosporin H (CsH), a specific inhibitor of FPR1, inhibited lung inflammation in the ALI models. Both MTDs and NFPs upon intratracheal challenge caused accumulation of neutrophils into the alveolar space with elevated BALF levels of mouse chemokine KC, interleukin-1β, and nitric oxide and increased pulmonary FPR-1 levels. CsH significantly attenuated MTDs or NFP-induced inflammatory lung injury and activation of MAPK and AKT pathways. FPR1 expression was present in rat primary alveolar epithelial type II cells (AECIIs) and was increased by MTDs. CsH inhibited MTDs or NFP-induced CINC-1/IL-8 release and phosphorylation of p38, JNK, and AKT in rat AECII and human cell line A549. Inhibitors of MAPKs and AKT also suppressed MTD-induced IL-8 release and NF-κB activation. Collectively, our data indicate an important role of the alveolar epithelium in initiating immune responses to MTDs released during ALI. The potential mechanism may involve increase of IL-8 production in MTD-activated AECII through FPR-1 and its downstream MAPKs, AKT, and NF-κB pathways.

scholarly journals Ancestral dietary change alters development of Drosophila larvae through MAPK signalling

2020 ◽  
Author(s):  
Samuel G. Towarnicki ◽  
Neil A. Youngson ◽  
Susan M. Corley ◽  
Jus C. St John ◽  
Nigel Turner ◽  
...  
Keyword(s):  
Disease Risk ◽  
Signalling Pathway ◽  
Transcriptional Analysis ◽  
Developmental Timing ◽  
Mapk Signalling Pathway ◽  
Developmental Growth ◽  
Drosophila Larvae ◽  
Mapk Signalling ◽  
Summary Statement

AbstractIncreasing evidence in animal species ranging from mammals to insects has revealed phenotypes that are caused by ancestral life experiences including stress and diet. The descendent phenotypes themselves are wide ranging, and include changes to behaviour, disease risk, metabolism, and growth. Ancestral dietary macronutrient composition, and quantity (over- and under-nutrition) have been shown to alter descendent growth, metabolism and behaviour. Several studies have identified inherited molecules in gametes which are altered by ancestral diet and are required for the transgenerational effect. However, there is less understanding of the developmental pathways in the period between fertilisation and adulthood that are altered by the inherited molecules. Here we identify a key role of the MAPK signalling pathway in mediating changes to Drosophila larval developmental timing due to variation in ancestral diet. We exposed grand-parental and great grand-parental generations to defined protein to carbohydrate (P:C) dietary ratios and measured developmental timing. Descendent developmental timing was consistently faster in the period between the embryonic and pupal stages when the ancestor had a higher P:C ratio diet. Transcriptional analysis of embryos, larvae and adults revealed extensive and long-lasting changes to the MAPK signalling pathway which controlled growth rate through regulation of ribosomal RNA transcription. The importance of these processes was supported by pharmacological inhibition of MAPK and rRNA proteins which reproduced the ancestral diet-induced developmental changes. This work provides insight into the role of developmental growth signalling networks in mediating non-genetic inheritance in the period between fertilisation and adult.Summary statementAncestral, diet-induced descendent developmental timing changes are caused by alteration of MAPK signalling pathways in the period between the embryo and pupal stages in Drosophila.

scholarly journals Endocan regulates acute lung inflammation through control of leukocyte diapedesis

2019 ◽  
Vol 127 (3) ◽  
pp. 668-678 ◽  
Author(s):  
Alexandre Gaudet ◽  
Lucie Portier ◽  
Méline Prin ◽  
Marie-Christine Copin ◽  
Anne Tsicopoulos ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Inflammation ◽  
Distress Syndrome ◽  
Human Leukocyte ◽  
Transendothelial Migration ◽  
Acute Lung Inflammation ◽  
Leukocyte Transendothelial Migration

Acute respiratory distress syndrome is a severe form of respiratory failure, occurring in up to 20% of patients admitted to the intensive care unit with sepsis. Dysregulated leukocyte diapedesis is a major contributor to acute respiratory distress syndrome. Endocan is a circulating proteoglycan that binds to the leukocyte integrin leukocyte functional antigen-1 and blocks its interaction with its endothelial ligand, ICAM-1. The objective of this study was to evaluate the role of endocan in the control of acute lung inflammation. In vitro, endocan inhibited human leukocyte transendothelial migration as well as ICAM-1-dependent migration but had a very mild effect on ICAM-1-dependent adhesion. Endocan also acted as an inhibitor of transendothelial migration of mouse leukocytes. The effect of systemic administration of recombinant human endocan was assessed in a model of acute lung inflammation in BALB/c mice. Treatment with endocan 1 h after intratracheal LPS challenge reduced the alveolar inflammatory response, diminished histological features of acute lung injury, and improved respiratory function. These results highlight the anti-inflammatory role of human endocan and its protective effect against acute lung injury. NEW & NOTEWORTHY We show here that endocan inhibits ICAM-1-dependent human leukocyte transendothelial migration and ICAM-1-dependent adhesion. We also found that in BALB/c mice with tracheal LPS-induced acute lung injury treatment with recombinant human endocan reduces lung inflammation, notably through reduction of neutrophilic recruitment, and restores normal lung function. These results confirm the hypothesis that human endocan may have a protective effect against acute lung inflammation.

scholarly journals Effects of NH4Cl intake on renal growth in rats: role of MAPK signalling pathway

2005 ◽  
Vol 20 (12) ◽  
pp. 2654-2660 ◽  
Author(s):  
Leda M. A. Bento ◽  
Jose B. C. Carvalheira ◽  
Leonardo F. Menegon ◽  
Mario J. A. Saad ◽  
Jose A. R. Gontijo
Keyword(s):  
Signalling Pathway ◽  
Renal Growth ◽  
Mapk Signalling Pathway ◽  
Mapk Signalling

scholarly journals Macrophage micro-RNA-155 promotes lipopolysaccharide-induced acute lung injury in mice and rats

2016 ◽  
Vol 311 (2) ◽  
pp. L494-L506 ◽  
Author(s):  
Wen Wang ◽  
Zhi Liu ◽  
Jie Su ◽  
Wen-Sheng Chen ◽  
Xiao-Wu Wang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Alveolar Macrophages ◽  
Lung Inflammation ◽  
Micro Rna ◽  
Pcr Analysis ◽  
Cytokine Signaling ◽  
Wild Type

Micro-RNA (miR)-155 is a novel gene regulator with important roles in inflammation. Herein, our study aimed to explore the role of miR-155 in LPS-induced acute lung injury(ALI). ALI in mice was induced by intratracheally delivered LPS. Loss-of-function experiments performed on miR-155 knockout mice showed that miR-155 gene inactivation protected mice from LPS-induced ALI, as manifested by preserved lung permeability and reduced lung inflammation compared with wild-type controls. Bone marrow transplantation experiments identified leukocytes, but not lung parenchymal-derived miR-155-promoted acute lung inflammation. Real-time PCR analysis showed that the expression of miR-155 in lung tissue was greatly elevated in wild-type mice after LPS stimulation. In situ hybridization showed that miR-155 was mainly expressed in alveolar macrophages. In vitro experiments performed in isolated alveolar macrophages and polarized bone marrow-derived macrophages confirmed that miR-155 expression in macrophages was increased in response to LPS stimulation. Conversely, miR-155 gain-of-function in alveolar macrophages remarkably exaggerated LPS-induced acute lung injury. Molecular studies identified the inflammation repressor suppressor of cytokine signaling (SOCS-1) as the downstream target of miR-155. By binding to the 3′-UTR of the SOCS-1 mRNA, miR-155 downregulated SOCS-1 expression, thus, permitting the inflammatory response during lung injury. Finally, we generated a novel miR-155 knockout rat strain and showed that the proinflammatory role of miR-155 was conserved in rats. Our study identified miR-155 as a proinflammatory factor after LPS stimulation, and alveolar macrophages-derived miR-155 has an important role in LPS-induced ALI.

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