October 9 - 12, 2012
Building 10 & Natcher Conference Center
- General Schedule of Events
- Opening Plenary Session
- Concurrent Symposia Sessions
- Poster Sessions
- National Graduate Student Research Conference
- FARE Award Ceremony
- Special Exhibits on Resources for Intramural Research
- TSA Research Festival Exhibit Show
- Clinical Center Tours
- Research Festival Committees
- Past Research Festivals
IL-6 induced epigenetic change promotes a mast cell hyper-responsive phenotype.
| Thursday, November 07, 2013 — Poster Session II | |||
|---|---|---|---|
12:00 p.m. – 2:00 p.m. |
FAES Academic Center (Upper-Level Terrace) |
NIAID |
CHEMCELL-5 |
Authors
- A.N. Desai
- M.Y Jung
- A.M. Gilfillan
- M.A. Beaven
- D.D. Metcalfe
Abstract
Mast cells (MC) release IL-6 in response to antigen, SCF and other stimulants. IL-6 in turn is known to promote MC maturation, activation, chemotaxis, and survival. To understand how IL-6 regulates mast cell responsiveness, we cultured mast cells in stem cell factor with or without IL-6. IL-6 alters cell morphology, and mast cells grown in the presence of IL-6 have more KIT high and Chymase high cells. Chronic exposure to IL-6 enhanced mast cell response to antigen, increased production of both IL-8 and GMCSF, and that the hypersensitivity to Ag is reversed after 7-14 days upon removal of IL-6. IL-6 increases production and activation of STAT3, which correlated with the hypermethylation of SOCS3 promoter in the 5’UTR region. Hyper methylation of the SOCS3 promoter was reversed after seven days upon removal of IL-6. These data are consistent with the conclusion that chronic exposure of mast cells to IL-6 results in the hypermethylation of the promoter region of the SOCS3 gene, thereby disrupting the autoregulatory mechanism of IL-6/JAK/STAT pathway, promoting a hyper-responsive phenotype. These observations suggest that interruption of the effects of IL-6 on human mast cells may provide a novel therapeutic approach for the treatment of mast cell dependent inflammation.
