LIGHT deficiency attenuates acute kidney disease development in an in vivo experimental renal ischemia and reperfusion injury model.

Ischemia-reperfusion (I/R), a leading risk factor of acute kidney injury (AKI), is associated with high mortality and risk of progression to chronic kidney disease. However, the molecular mechanism of I/R-AKI remains not fully understood, which hinders its efficient clinical treatment. In this study, we observed that LIGHT deficiency remarkably attenuated I/R-AKI, as evidenced by rescued renal function, ameliorated tubular cell apoptosis, and alleviated inflammatory responses.

Bone Marrow Mesenchymal Stem Cells Exert Protective Effects After Ischemic Stroke Through Upregulation of Glutathione.

Bone marrow mesenchymal stem cells (BMSCs) have been shown to promote stroke recovery, however, the underlying mechanisms are not well understood. In this study naïve rats were intravenously injected with syngeneic BMSCs to screen for potential differences in brain metabolite spectrum versus vehicle-treated controls by capillary electrophoresis-mass spectrometry. A total of 65 metabolites were significantly changed after BMSC treatment.

Tumor necrosis factor superfamily 14 is critical for the development of renal fibrosis.

Objective: Tumor necrosis factor superfamily protein 14 (TNFSF14) was recently identified as a risk factor in some fibrosis diseases. However, the role of TNFSF14 in renal fibrosis pathogenesis remains unknown.

Results: It was found that TNFSF14 levels were significantly increased both in UUO-induced renal fibrotic mice and in patients with fibrotic nephropathy, compared with those in controls.

LIGHT deficiency aggravates cisplatin-induced acute kidney injury by upregulating mitochondrial apoptosis.

Cisplatin is widely used as a chemotherapeutic agent for treating patients with solid tumors. The most common side effect of cisplatin treatment is nephrotoxicity. Recent studies have shown that mitochondrial apoptotic pathways are involved in cisplatin-induced acute kidney injury (Cis-AKI).

LIGHT aggravates sepsis-associated acute kidney injury via TLR4-MyD88-NF-κB pathway.

Sepsis-associated acute kidney injury (SA-AKI) is a common clinical critical care syndrome. It has received increasing attention due to its high morbidity and mortality; however, its pathophysiological mechanisms remain elusive. LIGHT, the 14th member of the tumour necrosis factor (TNF) superfamily and a bidirectional immunoregulatory molecule that regulates inflammation, plays a pivotal role in disease pathogenesis.

Fibrinogen-like protein 2 deficiency aggravates renal fibrosis by facilitating macrophage polarization.

Renal fibrosis has no effective target for its prevention or reversal. Fibinogen-like protein 2 (Fgl2) is a novel prothrombinase exhibiting coagulation activity and immunomodulatory effects. Although Fgl2 is known to play a vital role in the development of liver and interstitial fibrosis, its function in renal fibrosis remains unclear.

C5aR deficiency attenuates the breast cancer development via the p38/p21 axis.

Emerging evidence has shown activation of the complement component C5 to C5a in cancer tissues and C5aR expression in breast cancer cells relates to the tumor development and poor prognosis, suggesting the involvement of complement C5a/C5aR pathway in the breast cancer pathogenesis. In this study, we found that as compared to the non-tumoral tissues, both C5aR and MAPK/p38 showed an elevated expression, but p21/p-p21 showed lower expression, in the tumoral tissues of breast cancer patients. Mice deficient in C5aR or mice treated with the C5aR antagonist exhibited attenuation of breast cancer growth and reduction in the p38/p-p38 expression, but increase in p21/p-p21 expression, in the tumor tissues.

C5a/C5aR1 mediates IMQ-induced psoriasiform skin inflammation by promoting IL-17A production from γδ-T cells.

Psoriasis is a chronic relapsing inflammatory skin disease, affecting up to 3% of the global population. Accumulating evidence suggests that the complement system is involved in its pathogenesis. Our previous study revealed that the C5a/C5aR1 pathway is crucial for disease development.

Complement component 3 prevents imiquimod-induced psoriatic skin inflammation by inhibiting apoptosis in mice.

Complement component 3 (C3), a pivotal molecule in the complement system, is an essential immune mediator in various diseases, including psoriasis. However, the mechanistic role of C3 in psoriasis pathology and development remains elusive. Here, we showed that C3 deficiency dramatically augmented imiquimod-induced psoriasis-like skin inflammation, characterized by greater epidermal hyperplasia, inflammatory cell infiltration, and inflammatory gene expression than those in wild-type counterparts.

C5a/C5aR1 Pathway Is Critical for the Pathogenesis of Psoriasis.

Psoriasis is one of the most common chronic inflammatory skin diseases, affecting ~2% of the population. The lack of characterization of the pathogenesis of psoriasis has hindered efficient clinical treatment of the disease. In our study, we observed that expression of complement component 5a receptor 1(C5aR1) was significantly increased in skin lesions of both imiquimod (IMQ) and IL23-induced psoriatic mice and patients with psoriasis.

High expression of herpes virus entry mediator is associated with poor prognosis in clear cell renal cell carcinoma.

Herpes virus entry mediator (HVEM), also called tumor necrosis factor receptor superfamily 14 (TNFRSF14), is highly expressed in various tumor tissues and plays critical roles in tumor biology. However, the role of HVEM in clear cell renal cell carcinoma (ccRCC) is unknown. This study evaluated the clinical importance of HVEM in patients with ccRCC.

Celastrol alleviates renal fibrosis by upregulating cannabinoid receptor 2 expression.

Renal fibrosis is the final manifestation of various chronic kidney diseases, and no effective therapy is available to prevent or reverse it. Celastrol, a triterpene that derived from traditional Chinese medicine, is a known potent anti-fibrotic agent. However, the underlying mechanisms of action of celastrol on renal fibrosis remain unknown.

Complement C5a/C5aR pathway potentiates the pathogenesis of gastric cancer by down-regulating p21 expression.

Although the complement C5a/C5aR pathway is suggested to play a critical role in tumor pathogenesis, the underlying mechanism has yet to be fully elucidated. In the present study, we found that in patients with gastric cancer in different clinical stages (from stageâ… to stage â…£), both C5aR and p-PI3K/AKT levels were significantly higher in tumoral tissues than in adjacent non-tumoral tissues. In contrast, p21/p-p21 levels were significantly lower in tumoral tissues than in adjacent non-tumoral tissues.

C5a/C5aR pathway accelerates renal ischemia-reperfusion injury by downregulating PGRN expression.

Recent reports indicate that the complement C5a/C5aR pathway and progranulin (PGRN) deficiency both contribute to ischemia-reperfusion (IR)-induced acute kidney injury. However, the underlying relationship between the C5a/C5aR signaling pathway and PGRN expression during acute kidney injury is poorly understood. In this study, we showed that C5aR expression was significantly upregulated after renal IR, and that C5aR deficiency led to a marked increase in PGRN expression and a significant reduction in tubular damage and production of inflammatory cytokines.

Increased expression of Fibrinogen-Like Protein 2 is associated with poor prognosis in patients with clear cell renal cell carcinoma.

Fibrinogen-like protein 2 (FGL2) is highly expressed in various tumour tissues and plays a vital role in tumour initiation and progression. This study evaluated the clinical significance of FGL2 in patients with clear cell renal cell carcinoma (ccRCC). FGL2 expression in fresh and 170 archived paraffin-embedded ccRCC tissues was measured by quantitative RT-PCR, western blotting, and immunohistochemitry.

Complement component 3 deficiency prolongs MHC-II disparate skin allograft survival by increasing the CD4(+) CD25(+) regulatory T cells population.

Recent reports suggest that complement system contributes to allograft rejection. However, its underlying mechanism is poorly understood. Herein, we investigate the role of complement component 3 (C3) in a single MHC-II molecule mismatched murine model of allograft rejection using C3 deficient mice (C3(-/-)) as skin graft donors or recipients.

LIGHT/IFN-γ triggers β cells apoptosis via NF-κB/Bcl2-dependent mitochondrial pathway.

LIGHT recruits and activates naive T cells in the islets at the onset of diabetes. IFN-γ secreted by activated T lymphocytes is involved in beta cell apoptosis. However, whether LIGHT sensitizes IFNγ-induced beta cells destruction remains unclear.

STAT1-mediated down-regulation of Bcl-2 expression is involved in IFN-γ/TNF-α-induced apoptosis in NIT-1 cells.

Tumor necrosis factor (TNF)-α and interferon (IFN)-γ are the major pro-inflammatory cytokines involved in beta-cell destruction. The fate of islet beta-cells in the cytokine-induced intrinsic mitochondrial apoptotic pathway is determined by the interaction between members of the Bcl-2 family. However, the mechanism through which beta-cell apoptosis is regulated remains unclear.

C5a/C5aR pathway is essential for the pathogenesis of murine viral fulminant hepatitis by way of potentiating Fgl2/fibroleukin expression.

Unlabelled: Viral fulminant hepatitis (FH) remains a serious clinical problem with very high mortality. Lacking understanding of FH pathogenesis has in essence hindered efficient clinical treatment. Inferring from a correlation observed between the genetic differences in the complement component 5 (C5) and the susceptibility of mouse strains to murine hepatitis virus strain-3 (MHV-3) infections, we propose that excessive complement activation plays a critical role in the development of FH.

Caspase-3 is involved in IFN-γ- and TNF-α-mediated MIN6 cells apoptosis via NF-κB/Bcl-2 pathway.

TNF-α and IFN-γ are the major pro-inflammatory cytokines in the β-cell destruction. However, the underlying mechanism remains unclear. The present study used a murine insulinoma cell line MIN6 for further investigation of the effect of Caspase-3 on the cytokines-induced pancreatic β-cell apoptosis and analyzed the mechanisms involved in the activation of Caspase-3.

Growth of G422 glioma implanted in the mouse brain was affected by the immune ability of the host.

Background: It is generally accepted that gliomas are the most common primary brain tumors with poor prognosis. We aimed to explore the relationship of the immunity of the central nervous system and the genesis and development of glioma.

Methods: G422 glioma was implanted in the brain of BALB/c mice (immuno-competent mice), nude mice (T cell related immuno-deficient) and complement C3 knock-out mice (complement C3 related immunodeficient).

Induction of protective and therapeutic antitumor immunity by a DNA vaccine with C3d as a molecular adjuvant.

Although the critical role of complement component C3d as a molecular adjuvant in preventing virus infection is well established, its role in cancer therapies is unclear. In this study, we have engineered a DNA vaccine that expresses extracellular region of murine VEGFR-2 (FLK1(265-2493)) and 3 copies of C3d (C3d3), a component of complement as a molecular adjuvant, designed to increase antitumor immunity. VEGFR-2 has a more restricted expression on endothelial cells and is upregulated once these cells proliferate during angiogenesis in the tumor vasculature.

Construction of a DNA vaccine encoding Flk-1 extracellular domain and C3d fusion gene and investigation of its suppressing effect on tumor growth.

Although the critical role of complement component C3d as a molecular adjuvant in preventing virus infection is well established, its role in cancer prophylaxis and treatment is unclear. In this study, we constructed a recombinant plasmid encoding Flk-1 and C3d3 fusion proteins and investigated its transient expression in vitro in transfected eukaryotic cells and its antibody response in immunized mice. Subsequently, we investigated the vaccine's ability to elicit an immune response leading to suppression of angiogenesis and tumor growth in mice bearing bladder transitional cell carcinoma.

Mapping of binding epitopes of a human decay-accelerating factor monoclonal antibody capable of enhancing rituximab-mediated complement-dependent cytotoxicity.

Complement-dependent cytotoxicity (CDC) is thought to be one of the most important mechanisms of action of therapeutic monoclonal antibodies (mAbs). The decay-accelerating factor (DAF) overexpressed in certain tumors limits the CDC effect of the therapeutic anticancer antibodies. The use of DAF blocking antibodies targeted specifically at cancer cells in combination with immunotherapeutic mAbs of cancer may improve the therapeutic effect in cancer patients.

[Construction of C3b(AN42) and OVA(257-264) fusion gene and functional analysis of the fusion protein].

Aim: To explore the role of complement system in the T cell activation.

Methods: OVA(257-264) CTL epitope and C3b(AN42) encoding genes were synthesized and cloned into expression vector pEGFP-N1. COS-7 cells were transfected with the recombinant plasmid pEGFP-N1.