The interleukin-27 -964A&gt;G polymorphism enhances sepsis-induced inflammatory responses and confers susceptibility to the development of sepsis

He, Junbing; Zhang, Quanfu; Zhang, Wenying; Chen, Feng; Zhao, Tian; Lin, Yao; Li, Jia; Liu, Yuchun; Shao, Yiming

doi:10.1186/s13054-018-2180-0

Cited by 28 publications

(28 citation statements)

References 58 publications

(58 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sepsis is a systemic inflammatory disease resulting from a detrimental reaction to infection by pathogenic microorganisms. It has been demonstrated that the disruption of immune and inflammatory responses plays a key role in the pathogenesis of sepsis [3, 4]. Human immune cells are activated by pathogenic microorganisms and toxins and produce various inflammatory cytokines, leading to serious cell damage, microcirculatory disturbance, and organ dysfunction [24, 25].…”

Section: Discussionmentioning

confidence: 99%

“…Sepsis is defined as a systemic inflammatory reaction syndrome resulting from infection by various pathogenic microorganisms; it results in distressingly high morbidity and mortality in intensive care units (ICUs) throughout the world [1, 2]. Despite the unclear pathological mechanisms of sepsis, the progression of inflammatory cascades and the release of various proinflammatory mediators have been demonstrated to be involved in the pathogenesis and development of sepsis [3, 4]. A disintegrin and metalloproteinase 10 (ADAM10) is involved in the shedding of more than 40 cellular substrates, including CX3CL1, IL-6R, and TNF- α , and influences the release of the inflammatory cytokines IL-6 and IL-1 β in activated neutrophils, monocytes, and macrophages, which have been theorized to play pivotal roles in sepsis [5–7].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

miR-23b Negatively Regulates Sepsis-Induced Inflammatory Responses by Targeting ADAM10 in Human THP-1 Monocytes

Zhang

Xie

et al. 2019

Mediators of Inflammation

Self Cite

View full text Add to dashboard Cite

Background Previous studies have demonstrated pivotal roles of disintegrin and metalloproteinase 10 (ADAM10) in the pathogenesis of sepsis. MicroRNA- (miR-) 23b has emerged as an anti-inflammatory factor that prevents multiple autoimmune diseases. However, the underlying mechanisms of miR-23b in the regulation of ADAM10 and sepsis remain uncharacterized. Methods The expression levels of ADAM10 and miR-23b were detected by quantitative RT-PCR and western blot analysis. Cytokine production and THP-1 cell apoptosis were measured by enzyme-linked immunosorbent and annexin V apoptosis assays. Bioinformatics analyses and qRT-PCR, western blot, and luciferase reporter assays were performed to identify ADAM10 as the target gene of miR-23b. Results miR-23b expression was downregulated in the peripheral blood mononuclear cells of sepsis patients and LPS-induced THP-1 cells and was negatively correlated with the expression of ADAM10 and inflammatory cytokines. miR-23b regulated ADAM10 expression by directly binding to the 3′-UTR of ADAM10 mRNA. The overexpression of miR-23b alleviated the LPS-stimulated production of inflammatory cytokines (TNF-α, IL-1β, and IL-6) and apoptosis by targeting ADAM10 in THP-1 cells. The inhibitor or knockdown of ADAM10 elicited effects similar to those of miR-23b on THP-1 cells upon LPS stimulation. Conclusions The present study demonstrated that miR-23b negatively regulated LPS-induced inflammatory responses by targeting ADAM10. The molecular regulatory mechanism of miR-23b in ADAM10 expression and sepsis-induced inflammatory consequences may provide potential therapeutic targets for sepsis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

miR-23b Negatively Regulates Sepsis-Induced Inflammatory Responses by Targeting ADAM10 in Human THP-1 Monocytes

Zhang

Xie

et al. 2019

Mediators of Inflammation

Self Cite

View full text Add to dashboard Cite

show abstract

“…In humans, serum levels of IL-17 are predictive of the development of sepsis and mortality in poly-trauma patients (14) and mutations in the IL-17A gene are associated with increased susceptibility to infection caused by gram positive bacteria and mortality (15). The immunosuppressive cytokine IL-27 increases in the plasma of many septic patients (16–27) and has been shown to inhibit the differentiation of Th17 cells (16, 18, 19, 28–33). These results have been recapitulated in diverse models of sepsis in mice (34–38).…”

Section: Introduction To Sepsis and The Il-17/il-27/il-33 Axismentioning

confidence: 99%

IL-17, IL-27, and IL-33: A Novel Axis Linked to Immunological Dysfunction During Sepsis

2019

View full text Add to dashboard Cite

Sepsis is a major cause of morbidity and mortality worldwide despite numerous attempts to identify effective therapeutics. While some sepsis deaths are attributable to tissue damage caused by inflammation, most mortality is the result of prolonged immunosuppression. Ex vivo , immunosuppression during sepsis is evidenced by a sharp decrease in the production of pro-inflammatory cytokines by T cells and other leukocytes and increased lymphocyte apoptosis. This allows suppressive cytokines to exert a greater inhibitory effect on lymphocytes upon antigen exposure. While some pre-clinical and clinical trials have demonstrated utility in targeting cytokines that promote lymphocyte survival, this has not led to the approval of any therapies for clinical use. As cytokines with a more global impact on the immune system are also altered by sepsis, they represent novel and potentially valuable therapeutic targets. Recent evidence links interleukin (IL)-17, IL-27, and IL-33 to alterations in the immune response during sepsis using patient serum and murine models of peritonitis and pneumonia. Elevated levels of IL-17 and IL-27 are found in the serum of pediatric and adult septic patients early after sepsis onset and have been proposed as diagnostic biomarkers. In contrast, IL-33 levels increase in patient serum during the immunosuppressive stage of sepsis and remain high for more than 5 months after recovery. All three cytokines contribute to immunological dysfunction during sepsis by disrupting the balance between type 1, 2, and 17 immune responses. This review will describe how IL-17, IL-27, and IL-33 exert these effects during sepsis and their potential as therapeutic targets.

show abstract

“…As an inflammatory cytokine, IL-27 plays an important role in infection disease, promotes the inflammatory response of sepsis [ 36 ], and acts as a marker in predicting bacterial infection in critically ill children [ 37 ]. In addition, previous studies have shown IL-27 playing a role in liver injury or failure [ 11 , 38 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

Gadolinium Chloride Inhibits the Production of Liver Interleukin-27 and Mitigates Liver Injury in the CLP Mouse Model

Fan

Wang

et al. 2021

Mediators of Inflammation

View full text Add to dashboard Cite

Background. Liver macrophages play an important regulatory role in the inflammatory response of liver injury after severe infection. Interleukin- (IL-) 27 is an inflammatory cytokine that plays an important role in diseases caused by bacterial infection. However, the relationship between IL-27 and liver macrophages in liver injury after severe infection is not yet clear. Methods. A cecal ligation puncture (CLP) model was established in wild-type (WT) and IL-27 receptor- (WSX-1-) deficient (IL-27r-/-) mice, and recombinant IL-27 and gadolinium chloride (GdCl3) were injected into WT mice in the designated groups. The serum and liver IL-27, IL-6, tumor necrosis factor alpha (TNF-α), and IL-1β expression levels were evaluated by ELISA, quantitative PCR, or Western blotting; serum ALT and AST were detected by detection kits; and the severity of liver damage was evaluated by hematoxylin and eosin staining and the TUNEL assay of the liver tissue from the different groups. Liver macrophage polarization was evaluated by immunofluorescence. In addition, the polarization of peritoneal macrophage was evaluated by flow cytometry. Results. The serum and liver IL-27 expression levels were elevated in WT mice after CLP-induced severe infection, which were consistent with the changes in HE scores in the liver tissue. The levels of serum ALT, AST, liver IL-6, TNF-α, and IL-1β mRNA and liver pathological injury scores were further increased when pretreated with recombinant IL-27 in WT mice, but these levels were decreased in IL-27r−/− mice after CLP-induced severe infection compared to WT mice. In WT mice pretreated with GdCl3, liver pathological scores, serum ALT and AST, TUNEL-positive cell proportion from liver tissues, liver IL-27 expression, and the liver macrophages M1 polarization proportion decreased after CLP; however, the serum IL-27, IL-6, TNF-α, and IL-1β levels and the pathological lung and kidney scores were not significantly changed. When supplemented with exogenous IL-27, the liver pathological scores, serum ALT, AST, TUNEL-positive cell proportion of liver tissues, liver IL-27 expression, and the liver macrophage M1 polarization proportion increased. The in vitro, IL-27 expression increased in peritoneal macrophages when stimulated with LPS. Recombinant IL-27 together with LPS promoted the elevations in IL-6, TNF-α, and IL-1β levels in supernatant and the M1 polarization of peritoneal macrophages. Conclusion. IL-27 is an important cytokine in the inflammatory response to liver injury after severe infection. The reduction of liver injury by gadolinium chloride in severe infection mice models may relate to the inhibition of liver IL-27 production. These changes may be mainly related to the decrease of liver macrophages M1 polarization. IL-27 may have a positive feedback on these macrophages.

show abstract

The interleukin-27 -964A>G polymorphism enhances sepsis-induced inflammatory responses and confers susceptibility to the development of sepsis

Cited by 28 publications

References 58 publications

miR-23b Negatively Regulates Sepsis-Induced Inflammatory Responses by Targeting ADAM10 in Human THP-1 Monocytes

miR-23b Negatively Regulates Sepsis-Induced Inflammatory Responses by Targeting ADAM10 in Human THP-1 Monocytes

IL-17, IL-27, and IL-33: A Novel Axis Linked to Immunological Dysfunction During Sepsis

Gadolinium Chloride Inhibits the Production of Liver Interleukin-27 and Mitigates Liver Injury in the CLP Mouse Model

Contact Info

Product

Resources

About