The toll-like receptor-9 (TLR9) agonist cytosine phosphate guanine (CpG), activates hepatic stellate cells (HSCs) and mediates fibrosis. We investigated the TLR9 effects on lymphocyte/HSCs interactions. Liver fibrosis was induced in wild-type (WT) mice by intra-peritoneal carbon-tetrachloride (CCl4) induction for 6 weeks. Fibrotic groups were intravenously treated by a vehicle versus CpG along last 2 weeks. Compared to vehicle-treated fibrotic WT, the in-vivo CpG-treatment significantly attenuated hepatic fibrosis and inflammation, associated with decreased CD8 and increased NK liver cells. In-vitro, co-cultures with vehicle-treated fibrotic NK cells increased HSCs proliferation (P<0.001) while their CpG-treated counterparts achieved a significant decrease. To investigate the role of lymphocytes, TLR9(-/-) mice induced-hepatic fibrosis were used. Although TLR9(-/-) mice manifested lower fibrotic profile as compared to their wild-type (WT) counterparts, senescence (SA-β-Gal activity) in the liver and ALT serum levels were significantly greater. In an adoptive transfer model; irradiated WT and TLR9(-/-) recipients were reconstituted with naïve WT or TLR9(-/-) lymphocytes. The adoptive transfer of TLR9(-/-) versus WT lymphocytes led to increased fibrosis of WT recipients. TLR9(-/-) fibrotic recipients reconstituted with TLR9(-/-) or WT lymphocytes showed no changes in hepatic fibrosis severity or ALT serum levels. TLR9 activation had inconsistent effects on lymphocytes and HSCs. The net balance of TLR9 activation in WT, displayed significant anti-fibrotic activity, accompanied by CD8 suppression and increased NK-cells, activity and adherence to HSCs. The pro-fibrotic and pro-inflammatory properties of TLR9(-/-) lymphocytes fail to activate HSCs with an early senescence in TLR9(-/-) mice.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858328PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0082571PLOS

Publication Analysis

Top Keywords

toll-like receptor-9
8
vehicle-treated fibrotic
8
natural killer
4
killer cell-dependent
4
cell-dependent anti-fibrotic
4
anti-fibrotic pathway
4
pathway liver
4
liver injury
4
injury toll-like
4
receptor-9 toll-like
4

Similar Publications

Background: Recombinant Necator americanus Glutathione-S-Transferase-1 (Na-GST-1) formulated on Alhydrogel (Na-GST-1/Alhydrogel) is being developed to prevent anemia and other complications of N. americanus infection. Antibodies induced by vaccination with recombinant Na-GST-1 are hypothesized to interfere with the blood digestion pathway of adult hookworms in the host.

View Article and Find Full Text PDF

The neonatal period is a critical phase for the development of the intestinal immune system, marked by rapid adaptation to the external environment and unique nutritional demands. Breast milk plays a pivotal role in this transition, yet the mechanisms by which it influences neonatal mucosal immunity remain unclear. This review examines the potential mechanisms by which cell-free DNA (cfDNA) in breast milk may impact neonatal immune development, particularly through Toll-like receptor 9 (TLR9) signalling and gut microbiota interactions.

View Article and Find Full Text PDF

Osteogenic CpG Oligodeoxynucleotide, iSN40, Inhibits Osteoclastogenesis in a TLR9-Dependent Manner.

Life (Basel)

November 2024

Department of Agriculture, Graduate School of Science and Technology, Shinshu University, 8304 Minami-minowa, Kami-ina, Nagano 399-4598, Japan.

A CpG oligodeoxynucleotide (CpG-ODN), iSN40, was originally identified as promoting the mineralization and differentiation of osteoblasts, independent of Toll-like receptor 9 (TLR9). Since CpG ODNs are often recognized by TLR9 and inhibit osteoclastogenesis, this study investigated the TLR9 dependence and anti-osteoclastogenic effect of iSN40 to validate its potential as an osteoporosis drug. The murine monocyte/macrophage cell line RAW264.

View Article and Find Full Text PDF

Objective: To elucidate the association between the changes in intracellular metabolism in the early stage of B cell activation and systemic lupus erythematosus (SLE) pathogenesis.

Methods: CD19 or CD19CD27 (naïve) cells from the peripheral blood of healthy controls and lupus patients were cultured under different stimuli. The changes in intracellular metabolism and signalling pathways in these cells were evaluated.

View Article and Find Full Text PDF
Article Synopsis
  • Advances in fundus imaging are uncovering disruptions in the neurovascular unit related to diabetic retinopathy (DR), highlighting the need for a better understanding of neurodegeneration during anti-VEGF treatments.
  • Extracellular mitochondria are found to worsen retinal pigment epithelium (RPE) degeneration and inflammation in DR patients by increasing in the vitreous and are linked with visual impairment, but not other advanced retinopathy complications.
  • The study reveals that these mitochondria trigger cell death in RPE cells via a process dependent on mitochondrial DNA and induce inflammatory responses through specific receptors, positioning them as a critical factor in the worsening of RPE deterioration in DR.
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!