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

Jihye Lee, Tomoyuki Nakagiri, Takahiro Oto, Masaya Harada, Eiichi Morii, Yasushi Shintani, Masayoshi Inoue, Yoichiro Iwakura, Shinichiro Miyoshi, Meinoshin Okumura, Toshio Hirano, Masaaki Murakami

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1928-1936
Number of pages9
JournalJournal of Immunology
Volume189
Issue number4
DOIs
Publication statusPublished - Aug 15 2012

Fingerprint

Interleukin-6
Transplants
Graft Rejection
Collagen Type I
Heterotopic Transplantation
Bronchiolitis Obliterans
Th1 Cells
Chemotactic Factors
Homologous Transplantation
Chemokines
Epidermal Growth Factor
Autoimmune Diseases
Inflammation

ASJC Scopus subject areas

  • Immunology

Cite this

IL-6 amplifier, NF-κB-triggered positive feedback for IL-6 signaling, in grafts is involved in allogeneic rejection responses. / Lee, Jihye; Nakagiri, Tomoyuki; Oto, Takahiro; Harada, Masaya; Morii, Eiichi; Shintani, Yasushi; Inoue, Masayoshi; Iwakura, Yoichiro; Miyoshi, Shinichiro; Okumura, Meinoshin; Hirano, Toshio; Murakami, Masaaki.

In: Journal of Immunology, Vol. 189, No. 4, 15.08.2012, p. 1928-1936.

Research output: Contribution to journalArticle

Lee, J, Nakagiri, T, Oto, T, Harada, M, Morii, E, Shintani, Y, Inoue, M, Iwakura, Y, Miyoshi, S, Okumura, M, Hirano, T & Murakami, M 2012, 'IL-6 amplifier, NF-κB-triggered positive feedback for IL-6 signaling, in grafts is involved in allogeneic rejection responses', Journal of Immunology, vol. 189, no. 4, pp. 1928-1936. https://doi.org/10.4049/jimmunol.1103613
Lee, Jihye ; Nakagiri, Tomoyuki ; Oto, Takahiro ; Harada, Masaya ; Morii, Eiichi ; Shintani, Yasushi ; Inoue, Masayoshi ; Iwakura, Yoichiro ; Miyoshi, Shinichiro ; Okumura, Meinoshin ; Hirano, Toshio ; Murakami, Masaaki. / IL-6 amplifier, NF-κB-triggered positive feedback for IL-6 signaling, in grafts is involved in allogeneic rejection responses. In: Journal of Immunology. 2012 ; Vol. 189, No. 4. pp. 1928-1936.
@article{0faadd5235134b0cb66317382841bebf,
title = "IL-6 amplifier, NF-κB-triggered positive feedback for IL-6 signaling, in grafts is involved in allogeneic rejection responses",
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.",
author = "Jihye Lee and Tomoyuki Nakagiri and Takahiro Oto and Masaya Harada and Eiichi Morii and Yasushi Shintani and Masayoshi Inoue and Yoichiro Iwakura and Shinichiro Miyoshi and Meinoshin Okumura and Toshio Hirano and Masaaki Murakami",
year = "2012",
month = "8",
day = "15",
doi = "10.4049/jimmunol.1103613",
language = "English",
volume = "189",
pages = "1928--1936",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "4",

}

TY - JOUR

T1 - IL-6 amplifier, NF-κB-triggered positive feedback for IL-6 signaling, in grafts is involved in allogeneic rejection responses

AU - Lee, Jihye

AU - Nakagiri, Tomoyuki

AU - Oto, Takahiro

AU - Harada, Masaya

AU - Morii, Eiichi

AU - Shintani, Yasushi

AU - Inoue, Masayoshi

AU - Iwakura, Yoichiro

AU - Miyoshi, Shinichiro

AU - Okumura, Meinoshin

AU - Hirano, Toshio

AU - Murakami, Masaaki

PY - 2012/8/15

Y1 - 2012/8/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84864799416&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864799416&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1103613

DO - 10.4049/jimmunol.1103613

M3 - Article

C2 - 22798669

AN - SCOPUS:84864799416

VL - 189

SP - 1928

EP - 1936

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 4

ER -