Decreased PD-1/PD-L1 Expression Is Associated with the Reduction in Mucosal Immunoglobulin A in Mice with Intestinal Ischemia Reperfusion

Luo

2019

Med Sci Monit

Background The aim of this study was to investigate the clinical correlation between sPD-1 (soluble programmed cell death-1) and PD-1 (programmed cell death-1) expression and cancer pain. Material/Methods sPD-1 content in peripheral blood was determined by enzyme-linked immunosorbent assay (ELISA). T cell surface-positive rate was determined by flow cytometry, and the correlation of clinical characteristics of patients with cancer pain was analyzed. Results The positive expression rate of PD-1 in sPD-1 and T cells of patients with cancer pain was higher than that in normal patients. There was a significant correlation between sPD-1 and PD-1 positivity on T cell surface with tumor type, differentiation degree, and VAS scores of patients with cancer pain (P<0.05). Peripheral blood sPD-1 level and PD-1 positivity in patients with liver cancer and melanoma cancer were higher than those in patients with renal cell carcinoma and breast cancer. In addition, peripheral blood sPD-1 level and PD-1 positivity in patients with poorly-differentiated cancer pain were higher than those in patients with intermediately- to well-differentiated cancer. The sPD-1 content was lower and PD-1 positivity rate was higher in cancer pain patients with low VAS scores. Conclusions The positive expression rate of sPD-1 and PD-1 in patients with cancer pain is higher than that in normal people. The activation rate of the PD-1/PD-L1 pathway was mediated by sPD-1 and PD-1 positive expression, age, tumor type, and differentiation. There are correlations between clinical characteristics such as degree and pain level as shown by VAS score.

“…It is involved in programmed cell apoptosis and negatively regulates activated T lymphocytes. It is therefore considered an important cause of immunosuppression [17].…”

Section: Discussionmentioning

confidence: 99%

Association Between Activation of the Programmed Cell Death-1 (PD-1)/Programmed Death-Ligand 1 (PD-L1) Pathway and Pain in Patients with Cancer

Luo

2019

Med Sci Monit

“…At the end of the experiment, the mice were euthanized with an overdose of anaesthetic drugs. The I/R time was set as previously described [19]. Blood samples were obtained by cardiac puncture and were centrifuged at 3000 g for 10 min to separate the serum.…”

Section: Methodsmentioning

confidence: 99%

Pretreatment with the ALDH2 agonist Alda-1 reduces intestinal injury induced by ischaemia and reperfusion in mice

Zhu

Wang

et al. 2017

Clinical Science

Many studies demonstrate that activation of aldehyde dehydrogenase 2 (ALDH2) protects against oxidative stress via detoxification of cytotoxic aldehydes, and could attenuate cardiac, cerebral, lung and renal ischaemia–reperfusion (I/R) injuries. However, the effect of ALDH2 in intestinal I/R is unknown. The present study was set up to determine whether an ALDH2 agonist, Alda-1, could alleviate intestinal injury after gut I/R. In a mouse model of intestinal I/R injury, histological grading, proinflammatory cytokines, oxidative stress, cellular apoptosis, chemokine contents, ALDH2 activity, 4-hydroxy-trans-2-nonenal (4-HNE) and malondialdehyde (MDA) were evaluated. The results indicated that I/R treatment conferred elevation in pathological scores, proinflammatory cytokines, oxidative stress, cellular apoptosis and chemokine levels, accompanied by accumulated 4-HNE and MDA. No significant changes in ALDH2 activity were observed after I/R. However, Alda-1 pretreatment significantly decreased these injurious indicators, concomitant with up-regulated ALDH2 activity, and lessened 4-HNE and MDA accumulation. Taken together, our results implicate activation of ALDH2 by Alda-1 in the significant abatement intestinal I/R injury.

“…Gut mucosal immunoglobulin (Ig) A is critical for not only defending the host against pathogens but also regulating the host‐commensal relationship . However, we recently demonstrated that intestinal I/R resulted in impaired class switch recombination (CSR) of IgM B + cells, a key biological process involved in mucosal IgA synthesis, in peyer's patches (PPs) and decreased secretory IgA (sIgA) concentration in the gut lumen at 2 hrs after reperfusion . Transforming growth factor (TGF)‐β1, a polypeptide member of the TGF‐β superfamily, plays a pivotal role in cellular proliferation, differentiation and apoptosis as well as mucosal inflammation and immunity .…”

Section: Introductionmentioning

confidence: 99%

TGF‐β1 improves mucosal IgA dysfunction and dysbiosis following intestinal ischaemia–reperfusion in mice

Liu

J Cellular Molecular Medi

et al. 2016

Intestinal ischaemia/reperfusion (I/R) severely disrupts gut barriers and leads to high mortality in the critical care setting. Transforming growth factor (TGF)‐β1 plays a pivotal role in intestinal cellular and immune regulation. However, the effects of TGF‐β1 on intestinal I/R injury remain unclear. Thus, we aimed to investigate the effects of TGF‐β1 on gut barriers after intestinal I/R and the molecular mechanisms. Intestinal I/R model was produced in mice by clamping the superior mesenteric artery for 1 hr followed by reperfusion. Recombinant TGF‐β1 was intravenously infused at 15 min. before ischaemia. The results showed that within 2 hrs after reperfusion, intestinal I/R disturbed intestinal immunoglobulin A class switch recombination (IgA CSR), the key process of mucosal IgA synthesis, and resulted in IgA dysfunction, as evidenced by decreased production and bacteria‐binding capacity of IgA. Meanwhile, the disruptions of intestinal microflora and mucosal structure were exhibited. Transforming growth factor‐β1 activated IgA CSR as evidenced by the increased activation molecules and IgA precursors. Strikingly, TGF‐β1 improved intestinal mucosal IgA dysfunction, dysbiosis and epithelial damage at the early stage after reperfusion. In addition, SB‐431542, a specific inhibitor of activating mothers against decapentaplegic homologue (SMAD) 2/3, totally blocked the inductive effect of TGF‐β1 on IgA CSR and almost abrogated the above protective effects on intestinal barriers. Taken together, our study demonstrates that TGF‐β1 protects intestinal mucosal IgA immunity, microbiota and epithelial integrity against I/R injury mainly through TGF‐β receptor 1/SMAD 2/3 pathway. Induction of IgA CSR may be involved in the protection conferred by TGF‐β1.