Formylpeptide receptor 1 mediates the tumorigenicity of human hepatocellular carcinoma cells.

G protein-coupled chemoattractant receptors (GPCRs) have been implicated in cancer progression. Formylpeptide receptor 1 (FPR1) was originally identified as a GPCR mediating anti-microbial host defense. However, the role of FPR1 in tumorigenesis remains poorly understood.

Epigenetic silencing of JMJD5 promotes the proliferation of hepatocellular carcinoma cells by down-regulating the transcription of CDKN1A 686.

Proteins that contain jumonji C (JmjC) domains have recently been identified as major contributors to various malignant human cancers through epigenetic remodeling. However, the roles of these family members in the pathogenesis of hepatocellular carcinoma (HCC) are obscure. By mining public databases, we found that the HCC patients with lower JmjC domain-containing protein 5 (JMJD5) expression exhibited shorter survival time.

Hepatocyte-Specific Arid1a Deficiency Initiates Mouse Steatohepatitis and Hepatocellular Carcinoma.

ARID1A, encoding a subunit of chromatin remodeling SWI/SNF complexes, has recently been considered as a new type of tumor suppressor gene for its somatic mutations frequently found in various human tumors, including hepatocellular carcinoma (HCC). However, the role and mechanism of inactivated ARID1A mutations in tumorigenesis remain unclear. To investigate the role of ARID1A inactivation in HCC pathogenesis, we generated hepatocyte-specific Arid1a knockout (Arid1aLKO) mice by crossing mice carrying loxP-flanked Arid1a exon 8 alleles (Arid1af/f) with albumin promoter-Cre transgenic mice.

High glucose induces and activates Toll-like receptor 4 in endothelial cells of diabetic retinopathy.

Background: Hyperglycemia-induced inflammation causes the dysfunction of blood vessels, and Toll-like receptor 4 (TLR4) plays a key role in inflammation-induced angiogenesis. However, the impact of TLR4 on the pathogenesis of diabetic retinopathy (DR) is poorly understood. In this study, we examined the expression of TLR4 in retinal vascular endothelial cells of patients with DR and diabetic mice, and explored the role of TLR4 in mediating inflammatory responses by human microvascular endothelial cells (HMEC-1) under high-glucose condition.

Insulin receptor tyrosine kinase substrate activates EGFR/ERK signalling pathway and promotes cell proliferation of hepatocellular carcinoma.

Insulin receptor tyrosine kinase substrate (IRTKS) is closely associated with actin remodelling and membrane protrusion, but its role in the pathogenesis of malignant tumours, including hepatocellular carcinoma (HCC), is still unknown. In this study, we showed that IRTKS was frequently upregulated in HCC samples, and its expression level was significantly associated with tumour size. Enforced expression of IRTKS in human HCC cell lines significantly promoted their proliferation and colony formation in vitro, and their capacity to develop tumour xenografts in vivo, whereas knockdown of IRTKS resulted in the opposite effects.

The essential roles of Toll-like receptor signaling pathways in sterile inflammatory diseases.

Toll-like receptors (TLRs) form a family of pattern recognition receptors with at least 11 members in human and 13 in mouse. TLRs recognize a wide variety of putative host-derived agonists that have emerged as key mediators of innate immunity. TLR signaling also plays an important role in the activation of the adaptive immune system by inducing pro-inflammatory cytokines and upregulating costimulatory molecules of antigen presenting cells.

High-mobility group box-1 mediates toll-like receptor 4-dependent angiogenesis.

Objective: Inflammation is closely linked to angiogenesis, and Toll-like receptors (TLRs) are the key mediators of inflammatory responses. However, the impact of TLRs on angiogenesis is incompletely understood. In this study, we determined the involvement of TLRs in angiogenesis.

Impaired wound healing with defective expression of chemokines and recruitment of myeloid cells in TLR3-deficient mice.

Skin injury evokes both innate and adaptive immune responses to restore tissue integrity. TLRs play a critical role in host responses to injurious insults. Previous studies demonstrated that RNAs released from damaged tissues served as endogenous ligands for TLR3.

Production of recombinant human HMGB1 and anti-HMGB1 rabbit serum.

High-mobility group box-1 (HMGB1) plays important roles in inflammation, immune responses, and tumor progression. Since HMGB1 and its components have been shown to be mediators of a number of diseases but several sources of recombinant HMGB1 showed controversial biological activity, it is important to obtain recombinant HMGB1 with properties that resemble the native protein. For this purpose, we cloned genes coding for human HMGB1 and its active components A box and B box by PCR and inserted the cloned genes into pET28a vectors for transformation of Escherichia coli BL21.

HCV peptide (C5A), an amphipathic α-helical peptide of hepatitis virus C, is an activator of N-formyl peptide receptor in human phagocytes.

The hepatitis C virus (HCV) nonstructural 5A, a phosphorylated zinc metalloprotein, is an essential component of the HCV replication complex. An amphipathic α-helical peptide (HCV peptide [C5A]) derived from nonstructural 5A membrane anchor domain possesses potent anti-HCV and anti-HIV activity in vitro. In this study, we aimed to investigate the potential of HCV peptide (C5A) to regulate host immune responses.

The role of TLR2, TRL3, TRL4, and TRL9 signaling in the pathogenesis of autoimmune disease in a retinal autoimmunity model.

Purpose: Induction of tissue-specific experimental autoimmune diseases involves the use of complete Freund adjuvant containing Mycobacterium tuberculosis, whose recognition by the innate immune system depends on Toll-like receptors (TLRs) that signal through the adaptor molecule MyD88. The authors' previous study showed that MyD88(-/-) mice, but not TLR2(-/-), TLR4(-/-), or TLR9(-/-) mice, were resistant to experimental autoimmune uveitis (EAU).

Methods: The EAU induction in mice deficient in TLR3 or mice double deficient in TLR2+4, TLR2+9, and TLR4+9 was examined and the role of the TLR agonists in the adjuvant effect involved in the induction of EAU was assessed.