scholarly journals Gut-Lung Crosstalk in Sepsis-Induced Acute Lung Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Xin Zhou ◽  
Youxia Liao
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Distress Syndrome ◽  
Inflammatory Responses ◽  
Intestinal Barrier ◽  
Underlying Mechanism ◽  
Intestinal Microbiome ◽  
Mucosal Barrier ◽  
Intestinal Barrier Function ◽  
Lung Microbiome

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common acute and severe cases of the respiratory system with complicated pathogenesis and high mortality. Sepsis is the leading indirect cause of ALI/ARDS in the intensive care unit (ICU). The pathogenesis of septic ALI/ARDS is complex and multifactorial. In the development of sepsis, the disruption of the intestinal barrier function, the alteration of gut microbiota, and the translocation of the intestinal microbiome can lead to systemic and local inflammatory responses, which further alter the immune homeostasis in the systemic environment. Disruption of homeostasis may promote and propagate septic ALI/ARDS. In turn, when ALI occurs, elevated levels of inflammatory cytokines and the shift of the lung microbiome may lead to the dysregulation of the intestinal microbiome and the disruption of the intestinal mucosal barrier. Thus, the interaction between the lung and the gut can initiate and potentiate sepsis-induced ALI/ARDS. The gut–lung crosstalk may be a promising potential target for intervention. This article reviews the underlying mechanism of gut-lung crosstalk in septic ALI/ARDS.

scholarly journals Serinc2 deficiency causes susceptibility to sepsis-associated acute lung injury

2021 ◽  
Author(s):  
Shuai Mao ◽  
Jian Lv ◽  
Meng Chen ◽  
Ningning Guo ◽  
Yu Fang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Responses ◽  
Cecal Ligation ◽  
Underlying Mechanism ◽  
Raw264.7 Cells ◽  
Inflammatory Factors ◽  
High Morbidity ◽  
Positive Staining ◽  
Protective Effects

Abstract Background Severe sepsis and its subsequent complications cause high morbidity and mortality rates worldwide. Lung is one of the most vulnerable organs sensitive to sepsis-associated inflammatory storm, and usually develops into acute respiratory distress syndrome (ARDS)/acute lung injury (ALI). The pathogenesis of sepsis-associated ALI is accompanied by coordinated transmembrane signal transduction and subsequent programmed cell death; however, the underlying mechanism remains largely unclear. Results Here we find that the expression of serine incorporator 2 (Serinc2), a protein involved in phosphatidylserine synthesis and membrane incorporation, is upregulated in cecal ligation and puncture (CLP)-induced ALI. Furthermore, serinc2-knockout (KO) mouse line is generated by CRISPR-cas9 approach. Compared with wildtype mice, the Serinc2-KO mice exhibit exacerbated ALI-related pathologies after CLP. The expressions of pro-inflammatory factors, including IL1β, IL6, TNFα, and MCP1, are significantly enhanced by Serinc2 deficiency, concurrent with over-activation of STAT3, p38 and ERK pathways. Conversely, Serinc2 overexpression in RAW264.7 cells significantly suppresses the inflammatory responses induced by lipopolysaccharide (LPS). Serinc2 KO aggravates CLP-induced apoptosis as evidenced by increases in TUNEL-positive staining, Bax expression, and Caspase-3 cleavage and decreases in BCL-2 expression and Akt phosphorylation, whereas these changes are suppressed by Serinc2 overexpression in LPS-treated RAW264.7 cells. Moreover, administration of AKTin, an inhibitor of Akt, abolishes the protective effects of Serinc2 overexpression against inflammation and apoptosis. Conclusions Our findings demonstrate a protective role of Serinc2 in the lung through activating the Akt pathway, and provide novel insight into the pathogenesis of sepsis-induced ALI.

scholarly journals BAFF Blockade Attenuates Inflammatory Responses and Intestinal Barrier Dysfunction in a Murine Endotoxemia Model

2020 ◽  
Vol 11 ◽  
Author(s):  
Runze Quan ◽  
Chaoyue Chen ◽  
Wei Yan ◽  
Ying Zhang ◽  
Xi Zhao ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Survival Rates ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Barrier Dysfunction ◽  
Protein Levels ◽  
Lps Challenge ◽  
Endotoxemia Model

B cell-activating factor (BAFF) production is increased in septic patients. However, the specific role of BAFF in sepsis remains unknown. This study was designed to investigate the expression and function of BAFF in an experimental endotoxemia model and to identify the potential mechanisms. We established an endotoxemia mouse (6–8 weeks, 20–22 g) model by administering 30 mg/kg lipopolysaccharide (LPS). BAFF levels in the circulating system and organ tissues were measured 4 and 8 h after LPS injection. Survival rates in the endotoxemia mice were monitored for 72 h after BAFF blockade. The effects of BAFF blockade on systemic and local inflammation, organ injuries, and intestinal barrier function were also evaluated 4 h after LPS treatment. BAFF production was systemically and locally elevated after LPS challenge. BAFF blockade improved the survival rate, systemic inflammation, and multi-organ injuries. Moreover, BAFF blockade attenuated both intestinal inflammation and impaired intestinal permeability. BAFF blockade upregulated ZO-1 and occludin protein levels via the NF-κB/MLCK/MLC signaling pathway. These results suggested that BAFF blockade protects against lethal endotoxemia at least partially by alleviating inflammation, multi-organ injuries, and improving intestinal barrier function and provides a novel focus for further research on sepsis and experimental evidence for clinical therapy.

scholarly journals Trifostigmanoside I, an Active Compound from Sweet Potato, Restores the Activity of MUC2 and Protects the Tight Junctions through PKCα/β to Maintain Intestinal Barrier Function

2020 ◽  
Vol 22 (1) ◽  
pp. 291
Author(s):  
Amna Parveen ◽  
Seungho Choi ◽  
Ju-Hee Kang ◽  
Seung Hyun Oh ◽  
Sun Yeou Kim
Keyword(s):  
Tight Junctions ◽  
Sweet Potato ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Human Colon ◽  
Underlying Mechanism ◽  
Intestinal Barrier Function ◽  
Isolation And Identification ◽  
Human Colon Cancer ◽  
Mucin Production

Sweet potato (Ipomoea batata) is considered a superfood among vegetables and has been consumed for centuries. Traditionally, sweet potato is used to treat several illnesses, including diarrhea and stomach disorders. This study aimed to explore the protective effect of sweet potato on intestinal barrier function, and to identify the active compounds of sweet potato and their underlying mechanism of action. To this purpose, bioactivity-guided isolation, Western blotting, and immunostaining assays were applied. Interestingly, our bioactivity-guided approach enabled the first isolation and identification of trifostigmanoside I (TS I) from sweet potato. TS I induced mucin production and promoted the phosphorylation of PKCα/β in LS174T human colon cancer cells. In addition, it protected the function of tight junctions in the Caco-2 cell line. These findings suggest that TS I rescued the impaired abilities of MUC2, and protected the tight junctions through PKCα/β, to maintain intestinal barrier function.

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