Elevation of IL-6 in transgenic mice results in increased levels of the 90 kDA heat shock protein (hsp90) and the production of anti-hsp90 antibodies

Anastasis Stephanou, Susan Conroy, David A. Isenberg, Domenico Maione, Valeria Poli, Gennaro Ciliberto, David S. Latchman

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Treatment of human peripheral blood lymphocytes (PBL) in vitro with the cytokine interleukin-6 (IL-6) induces increased levels of the 90 kDa heat shock protein (hsp90). Hsp90 levels are also elevated in PBLs of human patients with systemic lupus erythematosus (SLE) and in MRL/lpr mice with autoimmune disease. Although IL-6 is elevated in both these situations it has not been shown that it is involved in stimulating elevation of hsp90 levels in vivo. Here we show directly that the elevation of IL-6 in vivo either in mice transgenic for the IL-6 gene or in knock-out mice lacking a functional gene for the transcription factor C/EBPβ (NF-IL-6) does indeed result in elevated hsp90 levels. This overexpression is associated with the specific production of autoantibodies to hsp90 in these mice which is also observed in SLE patients and MRL/lpr mice. Hence IL-6 is likely to play a critical role in the regulation of hsp90 levels both in autoimmune disease states and potentially in normal cells in vivo. In turn the elevated levels of hsp90 produced in autoimmune diseases are likely to be responsible for the observed production of anti-hsp90 autoantibodies.

Original languageEnglish
Pages (from-to)249-253
Number of pages5
JournalJournal of Autoimmunity
Volume11
Issue number3
DOIs
Publication statusPublished - Jun 1998

Fingerprint

HSP90 Heat-Shock Proteins
Transgenic Mice
Anti-Idiotypic Antibodies
Interleukin-6
Inbred MRL lpr Mouse
Autoimmune Diseases
Systemic Lupus Erythematosus
Autoantibodies
Knockout Mice
Genes
Transcription Factors
Lymphocytes
Cytokines

Keywords

  • Heat shock proteus
  • Hsp90
  • IL-6
  • Transgenic mice

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Elevation of IL-6 in transgenic mice results in increased levels of the 90 kDA heat shock protein (hsp90) and the production of anti-hsp90 antibodies. / Stephanou, Anastasis; Conroy, Susan; Isenberg, David A.; Maione, Domenico; Poli, Valeria; Ciliberto, Gennaro; Latchman, David S.

In: Journal of Autoimmunity, Vol. 11, No. 3, 06.1998, p. 249-253.

Research output: Contribution to journalArticle

Stephanou, Anastasis ; Conroy, Susan ; Isenberg, David A. ; Maione, Domenico ; Poli, Valeria ; Ciliberto, Gennaro ; Latchman, David S. / Elevation of IL-6 in transgenic mice results in increased levels of the 90 kDA heat shock protein (hsp90) and the production of anti-hsp90 antibodies. In: Journal of Autoimmunity. 1998 ; Vol. 11, No. 3. pp. 249-253.
@article{ceb8eddb2a004df8a1fc3f429ca09372,
title = "Elevation of IL-6 in transgenic mice results in increased levels of the 90 kDA heat shock protein (hsp90) and the production of anti-hsp90 antibodies",
abstract = "Treatment of human peripheral blood lymphocytes (PBL) in vitro with the cytokine interleukin-6 (IL-6) induces increased levels of the 90 kDa heat shock protein (hsp90). Hsp90 levels are also elevated in PBLs of human patients with systemic lupus erythematosus (SLE) and in MRL/lpr mice with autoimmune disease. Although IL-6 is elevated in both these situations it has not been shown that it is involved in stimulating elevation of hsp90 levels in vivo. Here we show directly that the elevation of IL-6 in vivo either in mice transgenic for the IL-6 gene or in knock-out mice lacking a functional gene for the transcription factor C/EBPβ (NF-IL-6) does indeed result in elevated hsp90 levels. This overexpression is associated with the specific production of autoantibodies to hsp90 in these mice which is also observed in SLE patients and MRL/lpr mice. Hence IL-6 is likely to play a critical role in the regulation of hsp90 levels both in autoimmune disease states and potentially in normal cells in vivo. In turn the elevated levels of hsp90 produced in autoimmune diseases are likely to be responsible for the observed production of anti-hsp90 autoantibodies.",
keywords = "Heat shock proteus, Hsp90, IL-6, Transgenic mice",
author = "Anastasis Stephanou and Susan Conroy and Isenberg, {David A.} and Domenico Maione and Valeria Poli and Gennaro Ciliberto and Latchman, {David S.}",
year = "1998",
month = "6",
doi = "10.1006/jaut.1998.0194",
language = "English",
volume = "11",
pages = "249--253",
journal = "Journal of Autoimmunity",
issn = "0896-8411",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Elevation of IL-6 in transgenic mice results in increased levels of the 90 kDA heat shock protein (hsp90) and the production of anti-hsp90 antibodies

AU - Stephanou, Anastasis

AU - Conroy, Susan

AU - Isenberg, David A.

AU - Maione, Domenico

AU - Poli, Valeria

AU - Ciliberto, Gennaro

AU - Latchman, David S.

PY - 1998/6

Y1 - 1998/6

N2 - Treatment of human peripheral blood lymphocytes (PBL) in vitro with the cytokine interleukin-6 (IL-6) induces increased levels of the 90 kDa heat shock protein (hsp90). Hsp90 levels are also elevated in PBLs of human patients with systemic lupus erythematosus (SLE) and in MRL/lpr mice with autoimmune disease. Although IL-6 is elevated in both these situations it has not been shown that it is involved in stimulating elevation of hsp90 levels in vivo. Here we show directly that the elevation of IL-6 in vivo either in mice transgenic for the IL-6 gene or in knock-out mice lacking a functional gene for the transcription factor C/EBPβ (NF-IL-6) does indeed result in elevated hsp90 levels. This overexpression is associated with the specific production of autoantibodies to hsp90 in these mice which is also observed in SLE patients and MRL/lpr mice. Hence IL-6 is likely to play a critical role in the regulation of hsp90 levels both in autoimmune disease states and potentially in normal cells in vivo. In turn the elevated levels of hsp90 produced in autoimmune diseases are likely to be responsible for the observed production of anti-hsp90 autoantibodies.

AB - Treatment of human peripheral blood lymphocytes (PBL) in vitro with the cytokine interleukin-6 (IL-6) induces increased levels of the 90 kDa heat shock protein (hsp90). Hsp90 levels are also elevated in PBLs of human patients with systemic lupus erythematosus (SLE) and in MRL/lpr mice with autoimmune disease. Although IL-6 is elevated in both these situations it has not been shown that it is involved in stimulating elevation of hsp90 levels in vivo. Here we show directly that the elevation of IL-6 in vivo either in mice transgenic for the IL-6 gene or in knock-out mice lacking a functional gene for the transcription factor C/EBPβ (NF-IL-6) does indeed result in elevated hsp90 levels. This overexpression is associated with the specific production of autoantibodies to hsp90 in these mice which is also observed in SLE patients and MRL/lpr mice. Hence IL-6 is likely to play a critical role in the regulation of hsp90 levels both in autoimmune disease states and potentially in normal cells in vivo. In turn the elevated levels of hsp90 produced in autoimmune diseases are likely to be responsible for the observed production of anti-hsp90 autoantibodies.

KW - Heat shock proteus

KW - Hsp90

KW - IL-6

KW - Transgenic mice

UR - http://www.scopus.com/inward/record.url?scp=0031855078&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031855078&partnerID=8YFLogxK

U2 - 10.1006/jaut.1998.0194

DO - 10.1006/jaut.1998.0194

M3 - Article

VL - 11

SP - 249

EP - 253

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

SN - 0896-8411

IS - 3

ER -