Identification of gp96 as a novel target for treatment of autoimmune disease in mice

Jung Min Han, Nam Hoon Kwon, Jin Young Lee, Seung Jae Jeong, Hee Jung Jung, Hyeong Rae Kim, Zihai Li, Sunghoon Kim

Research output: Contribution to journalArticle

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Abstract

Heat shock proteins have been implicated as endogenous activators for dendritic cells (DCs). Chronic expression of heat shock protein gp96 on cell surfaces induces significant DC activations and systemic lupus erythematosus (SLE)-like phenotypes in mice. However, its potential as a therapeutic target against SLE remains to be evaluated. In this work, we conducted chemical approach to determine whether SLE-like phenotypes can be compromised by controlling surface translocation of gp96. From screening of chemical library, we identified a compound that binds and suppresses surface presentation of gp96 by facilitating its oligomerization and retrograde transport to endoplasmic reticulum. In vivo administration of this compound reduced maturation of DCs, populations of antigen presenting cells, and activated B and T cells. The chemical treatment also alleviated the SLE-associated symptoms such as glomerulonephritis, proteinuria, and accumulation of anti-nuclear and -DNA antibodies in the SLE model mice resulting from chronic surface exposure of gp96. These results suggest that surface translocation of gp96 can be chemically controlled and gp96 as a potential therapeutic target to treat autoimmune disease like SLE.

Original languageEnglish
Article numbere9792
JournalPloS one
Volume5
Issue number3
DOIs
Publication statusPublished - 2010 Dec 1

Fingerprint

lupus erythematosus
autoimmune diseases
Systemic Lupus Erythematosus
Autoimmune Diseases
mice
dendritic cells
Dendritic Cells
Heat-Shock Proteins
heat shock proteins
Oligomerization
T-cells
Small Molecule Libraries
Phenotype
phenotype
glomerulonephritis
therapeutics
antigen-presenting cells
Antinuclear Antibodies
chemical treatment
Antigen-Presenting Cells

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Han, J. M., Kwon, N. H., Lee, J. Y., Jeong, S. J., Jung, H. J., Kim, H. R., ... Kim, S. (2010). Identification of gp96 as a novel target for treatment of autoimmune disease in mice. PloS one, 5(3), [e9792]. https://doi.org/10.1371/journal.pone.0009792
Han, Jung Min ; Kwon, Nam Hoon ; Lee, Jin Young ; Jeong, Seung Jae ; Jung, Hee Jung ; Kim, Hyeong Rae ; Li, Zihai ; Kim, Sunghoon. / Identification of gp96 as a novel target for treatment of autoimmune disease in mice. In: PloS one. 2010 ; Vol. 5, No. 3.
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Han, JM, Kwon, NH, Lee, JY, Jeong, SJ, Jung, HJ, Kim, HR, Li, Z & Kim, S 2010, 'Identification of gp96 as a novel target for treatment of autoimmune disease in mice', PloS one, vol. 5, no. 3, e9792. https://doi.org/10.1371/journal.pone.0009792

Identification of gp96 as a novel target for treatment of autoimmune disease in mice. / Han, Jung Min; Kwon, Nam Hoon; Lee, Jin Young; Jeong, Seung Jae; Jung, Hee Jung; Kim, Hyeong Rae; Li, Zihai; Kim, Sunghoon.

In: PloS one, Vol. 5, No. 3, e9792, 01.12.2010.

Research output: Contribution to journalArticle

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