The role of glycoprotein 96 in the persistent inflammation of rheumatoid arthritis

Qi Quan Huang, Richard M. Pope*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

19 Scopus citations


The 96-kDa glycoprotein (gp96) is an endoplasmic reticulum (ER) resident molecular chaperone. Under physiologic conditions, gp96 facilitates the transport of toll-like receptors (TLRs) to cell or endosomal membranes. Under pathologic circumstances such as rheumatoid arthritis, gp96 translocates to the cell surface and extracellular space, serving as an endogenous danger signal promoting TLR signaling. Macrophages play a central role in regulating innate and adaptive immunity, and are the major source of proinflammatory cytokines and chemokines in rheumatoid arthritis (RA). Macrophage numbers in the sublining of RA synovial tissue correlate with clinical response. This review focuses on the recent findings that implicate gp96 induced macrophage activation mediated through TLR signaling in the pathogenesis of RA and provides insights concerning the targeting gp96 and the TLR signaling pathway as therapeutic approaches for patients with RA and possibly other chronic inflammatory conditions.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalArchives of biochemistry and biophysics
Issue number1
StatePublished - Feb 1 2013


  • Endogenous ligands
  • Heat shock proteins
  • Rheumatoid arthritis
  • Toll like receptor

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology


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