IL10 Gene | ScienceGate

Angiotensin (Ang) II is well-known to have potent pro-oxidant and pro-inflammatory effects in the brain. Extensive crosstalk between the primary Ang II receptor, Ang type 1 receptor (AT1R), and the cannabinoid type 1 receptor (CB1R) has been demonstrated by various groups in the last decade. Since activation of glial CB1R has been demonstrated to play a key role in the resolution of inflammatory states, we investigated the role of Ang II (100 nM) and/or ACEA (10 nM), a potent CB1R-specific agonist in the regulation of inflammatory markers in astrocytes from spontaneously hypertensive rats (SHR) and Wistar rats. Astrocytes were cultured from brainstems and cerebellums of SHR and Wistar rats and assayed for IL1β and IL10 gene expression and secreted fraction, in treated and non-treated cells, by employing qPCR and ELISA, respectively. mRNA expression of both IL10 and IL1β were significantly elevated in untreated brainstem and cerebellar astrocytes isolated from SHR when compared to Wistar astrocytes. No changes were observed in the secreted fraction. While ACEA-treatment resulted in a significant increase in IL10 gene expression in Wistar brainstem astrocytes (Log2FC ≥ 1, p < 0.05), its effect in SHR brainstem astrocytes was diminished. Ang II treatment resulted in a strong inhibitory effect on IL10 gene expression in astrocytes from both brain regions of SHR and Wistar rats (Log2FC ≤ −1, p < 0.05), and an increase in IL1β gene expression in brainstem astrocytes from both strains (Log2FC ≥ 1, p < 0.05). Co-treatment of Ang II and ACEA resulted in neutralization of Ang II-mediated effect in Wistar brainstem and cerebellar astrocytes, but not SHR astrocytes. Neither Ang II nor ACEA resulted in any significant changes in IL10 or IL1β secreted proteins. These data suggest that Ang II and ACEA have opposing roles in the regulation of inflammatory gene signature in astrocytes isolated from SHR and Wistar rats. This however does not translate into changes in their secreted fractions.

Download Full-text

Mapping of the human IL10 gene and further characterization of the 5' flanking sequence

Immunogenetics ◽

10.1007/s002510050250 ◽

1997 ◽

Vol 46 (2) ◽

pp. 120-128 ◽

Cited By ~ 239

Author(s):

J. Eskdale ◽

Dieter Kube ◽

Hans Tesch ◽

Grant Gallagher

Keyword(s):

Flanking Sequence ◽

Il10 Gene ◽

Human Il10

Download Full-text

IL10 gene polymorphisms are associated with asthma phenotypes in children

Genetic Epidemiology ◽

10.1002/gepi.10298 ◽

2004 ◽

Vol 26 (2) ◽

pp. 155-165 ◽

Cited By ~ 63

Author(s):

Helen Lyon ◽

Christoph Lange ◽

Stephen Lake ◽

Edwin K. Silverman ◽

Adrienne G. Randolph ◽

...

Keyword(s):

Gene Polymorphisms ◽

Asthma Phenotypes ◽

Il10 Gene

Download Full-text

IL10-592 CC Genotype In the Donor Is Associated with a Significant Decrease of Relapse Rate and a Significant Increase of Event-Free Survival and Overall Survival After Allogeneic Hematopoietic Stem Cell Transplantation In Children with Hematological Malignancies

Blood ◽

10.1182/blood.v118.21.4459.4459 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4459-4459

Author(s):

Bernd Gruhn ◽

Janine Voigt ◽

Nadine Pfaffendorf-Regler ◽

Ilona Wolff ◽

Felix Zintl ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Relapse Rate ◽

Myeloid Leukemia ◽

Event Free Survival ◽

Hematopoietic Stem ◽

Free Survival ◽

Il10 Gene

Abstract Abstract 4459 IL10 is a pivotal immunomodulatory cytokine and is usually regarded as a suppressor of the immune responses. However, IL10 has been shown to have some immunostimulatory effects. The IL10-592 CC genotype is associated wit higher production of IL10. Because IL10 may promote the development of alloimmunity we hypothesized that the IL10-592 CC genotype in the donor reduces the risk of relapse after hematopoietic stem cell transplantation (HSCT). A cohort of 211 children (median age, 12 years) with acute lymphoblastic leukemia (n=100), acute myeloid leukemia (n=62), myelodysplastic syndrome (n=30) or chronic myeloid leukemia (n=19) who underwent allogeneic bone marrow (n=153) or peripheral blood stem cell transplantation (n=58; T-cell depleted: n=26) in a single center and/or their respective donors was genotyped of IL10 gene for rs1800872 using TaqMan real-time polymerase chain reaction. The donor was HLA-matched unrelated in 48% of transplants and HLA-identical related in 42% of transplants. Conditioning regimen was myeloablative in all cases. Two forms of post-transplant immunosuppression predominated, cyclosporine A and methotrexate in 69% of transplants and cyclosporine A alone in 17% of transplants. Cell samples from the donor were available in 174 cases and from the patient in 197 cases. The IL10-592 CC genotype was present in 82 of the 174 donors (47.1%) and in 104 of the 197 patients (52.8%). Interestingly, we found a significantly reduced incidence of relapse in patients who were transplanted from a donor with the IL10-592 CC genotype (15.9% versus 30.4%; p=0.016). In addition, we observed a significant increase of event-free survival (52.4% versus 33.7%; p=0.019) and a significant increase of overall survival (54.9% versus 37.0%; p=0.040) if the IL10-592 CC genotype was present in the donor. The occurrence of the IL10-592 CC genotype, in either donors or recipients, had no significant impact on treatment related mortality, acute and chronic graft-versus host disease. In conclusion, IL10-592 CC genotype in the donor is associated with a significant decrease of relapse rate and a significant increase of event-free survival and overall survival after HSCT in children with hematological malignancies. This is the first study to describe an association of IL10 gene polymorphism with relapse rate after HSCT. Selecting a donor with the IL10-592 CC genotype could be a useful therapeutic strategy for improving the final outcome after allogeneic HSCT. Disclosures: No relevant conflicts of interest to declare.

Download Full-text