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J Immunol. 2012 Aug 15;189(4):1928-36. doi: 10.4049/jimmunol.1103613. Epub 2012 Jul 13.

IL-6 amplifier, NF-κB-triggered positive feedback for IL-6 signaling, in grafts is involved in allogeneic rejection responses.

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1
Laboratory of Developmental Immunology, Japan Science and Technology Agency Core Research for Engineering, Science, and Technology, Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871, Japan.

Erratum in

  • J Immunol. 2012 Dec 15;189(12):5997.

Abstract

The IL-6-amplifier first was discovered as a synergistic activation mechanism for NF-κB/STAT3 in type 1 collagen(+) cells. This process is marked by the hyperinduction of chemokines and subsequent local inflammation that leads to autoimmune diseases. In this study, we show that IL-6 amplifier activation in grafts plays important roles in allogeneic graft rejection by using a tracheal heterotopic transplantation model that includes bronchiolitis obliterans, a pathological marker for chronic rejection. IL-6, epidermal growth factor, and IFN-γ all stimulate IL-6 amplifier activation, whereas CCL2, a chemotactic factor for Th1 cells, was one of the amplifier's main targets. Interestingly, IFN-γ hyperinduced CCL2 in type 1 collagen(+) cells via the IL-6 amplifier at least in vitro. In addition, we detected IL-6, CCL2, phospho-STAT3, and phospho-NF-κB in epithelial type 1 collagen(+) cells of allogeneic tracheal grafts. These results show that IL-6 amplifier activation in grafts plays a critical role for graft rejection responses after allogeneic transplantation, including chronic rejection. From these results, we consider whether the IL-6 amplifier in grafts might be a valuable therapeutic target for the prevention of transplant rejection, including chronic rejection.

PMID:
22798669
DOI:
10.4049/jimmunol.1103613
[Indexed for MEDLINE]
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