Beta-Defensin 2 and 3 Promote Bacterial Clearance of Pseudomonas aeruginosa by Inhibiting Macrophage Autophagy through Downregulation of Early Growth Response Gene-1 and c-FOS

Wu, Yongjian; Li, Dandan; Wang, Yi; Liu, Xi; Zhang, Yuanqing; Qu, Wenting; Chen, Kang; Francisco, Ngiambudulu M.; Feng, Lianqiang; Huang, Xi; Wu, Minhao

doi:10.3389/fimmu.2018.00211

Cited by 35 publications

(24 citation statements)

References 57 publications

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“…In addition, in the infected cornea of mice, silencing of the murine orthologues of HBD2 and 3 resulted in increased production of proinflammatory cytokines, with a simultaneous increase in bacterial load (91). The effect on bacterial load is postulated to be due to the defensins [at low concentration of 1 µg/ml (0.2 µM)] inhibiting macrophage autophagy and in this way increasing phagocytic receptor expression leading to intracellular killing of the Pseudomonas aeruginosa (92). All these studies indicate that, under specific infections scenarios, defensins are capable of contributing to antiinflammatory response, or at least a rebalancing of the nature of the cellular response.…”

Section: Innate Suppressionmentioning

confidence: 99%

The Dichotomous Responses Driven by β-Defensins

2020

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Defensins are short, rapidly evolving, cationic antimicrobial host defence peptides with a repertoire of functions, still incompletely realised, that extends beyond direct microbial killing. They are released or secreted at epithelial surfaces, and in some cases, from immune cells in response to infection and inflammation. Defensins have been described as endogenous alarmins, alerting the body to danger and responding to inflammatory signals by promoting both local innate and adaptive systemic immune responses. However, there is now increasing evidence that they exert variable control on the response to danger; creating a dichotomous response that can suppress inflammation in some circumstances but exacerbate the response to danger and damage in others and, at higher levels, lead to a cytotoxic effect. Focussing in this review on human β-defensins, we discuss the evidence for their functions as proinflammatory, immune activators amplifying the response to infection or damage signals and/or as mediators of resolution of damage, contributing to a return to homeostasis. Finally, we consider their involvement in the development of autoimmune diseases.

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Section: Innate Suppressionmentioning

confidence: 99%

The Dichotomous Responses Driven by β-Defensins

2020

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“…Western blot was performed as described previously (28). Cells were rinsed three times with ice-cold PBS (pH 7.4) and treated with lysis buffer containing 1% (v/v) protease inhibitor mixture, 1 mM phenylmethylsulphonyl fluoride, and 1 mM DTT.…”

Section: Western Blotmentioning

confidence: 99%

Activation-Induced Cell Death of Mucosal-Associated Invariant T Cells Is Amplified by OX40 in Type 2 Diabetic Patients

Zhang

Ming

Gong

et al. 2019

The Journal of Immunology

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Mucosal-associated invariant T (MAIT) cells play a key role in local and systemic immune responses. Studies suggest that type 2 diabetes (T2D) is associated with alterations in the human MAIT cell response. However, the mechanisms that regulate the survival and homeostasis of human MAIT cells are poorly defined. In this study, we demonstrate that the costimulatory TNF superfamily receptor OX40 was highly expressed in MAIT cells of patients with T2D. Compared with OX40-negative MAIT cells, OX40-positive MAIT cells showed a high activation and a memory phenotype. Surprisingly, OX40 expression was negatively correlated with the frequency of MAIT cells in the peripheral blood of T2D patients. Increased cleaved caspase-3 levels were observed in OX40 +expressing MAIT cells in T2D patients. In vitro, activated OX40 signaling by recombinant OX40L protein promoted caspase-3 activation and apoptosis of MAIT cells. Inhibition of caspase-3 restored apoptosis of MAIT cells induced by OX40 signaling. These results identify OX40 as an amplifier of activation-induced cell death of human blood MAIT cells and shed new light on the regulation of MAIT cells in the phase of immune responses in T2D.

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“…Considering that c-fos and ERK pathway also have been found to join in the regulation of cell autophagy (Wu et al. 2018; Fung and Liu 2019), the findings of our research suggested that up-regulation of MEG3 attended to the influence of morphine on HT22 cell autophagy might be achieved by elevating c-fos expression and promoting ERK pathway activation.…”

Section: Discussionmentioning

confidence: 52%

Long non-coding RNA MEG3 attends to morphine-mediated autophagy of HT22 cells through modulating ERK pathway

Gao

2019

Pharmaceutical Biology

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Context: Morphine is an alkaloid isolated from the poppy plants. The addiction of morphine is a very serious social issue. Some long non-coding RNAs (lncRNAs) have been proposed to engage in drug addiction. Objective: Whether lncRNA maternally expressed gene 3 (MEG3) attended to morphine-mediated autophagy of mouse hippocampal neuronal HT22 cells was probed. Materials and methods: HT22 cells were subjected to 10 µM morphine for 24 h. Cell autophagy was assessed by measuring LC3-II/LC3-I and Beclin-1 expression. qRT-PCR was carried out to measure MEG3 expression. SiRNA oligoribonucleotides targeting MEG3 (si-MEG3) was transfected to silence MEG3. The orexin1 receptor (OX1R), c-fos, p/t-ERK and p/t-PKC expressions were tested by western blotting. SCH772984 was used as an inhibitor of ERK pathway. Results: Morphine elevated OX1R (2.92 times), c-fos (2.06 times), p/t-ERK (2.04 times) and p/t-PKC (2.4 times), Beclin-1 (3.2 times) and LC3-II/LC3-I (3.96 times) expression in HT22 cells. Moreover, followed by morphine exposure, the MEG3 expression was also elevated in HT22 cells (3.03 times). The silence of MEG3 lowered the Beclin-1 (1.85 times), LC3-II/LC3-I (2.12 times), c-fos (1.39 times) and p/t-ERK (1.44 times) expressions in morphine-treated HT22 cells. Inhibitor of ERK pathway SCH772984 further promoted the influence of MEG3 silence on morphine-caused Beclin-1 (1.97 times) and LC3-II/LC3-I (1.92 times) expressions decreases. Conclusions: Up-regulation of MEG3 attended to the morphine-caused autophagy of HT22 cells might be through elevating c-fos expression and promoting ERK pathway activation. More experiments are also needed in the future to analyse the influence of other lncRNAs in drug addiction.

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Beta-Defensin 2 and 3 Promote Bacterial Clearance of Pseudomonas aeruginosa by Inhibiting Macrophage Autophagy through Downregulation of Early Growth Response Gene-1 and c-FOS

Cited by 35 publications

References 57 publications

The Dichotomous Responses Driven by β-Defensins

The Dichotomous Responses Driven by β-Defensins

Activation-Induced Cell Death of Mucosal-Associated Invariant T Cells Is Amplified by OX40 in Type 2 Diabetic Patients

Long non-coding RNA MEG3 attends to morphine-mediated autophagy of HT22 cells through modulating ERK pathway

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