Document Detail

Induction of heat shock protein gp96 by immune cytokines.
MedLine Citation:
PMID:  14984057     Owner:  NLM     Status:  MEDLINE    
Cytokines play a major role in regulating both humoral and cell-mediated immune responses. Recent advances in our understanding of cell-mediated immune responses have focused on the antigen presentation machinery and the proteins in the endoplasmic reticulum (ER). These proteins help the formation and stabilization of the major histocompatibility complex (MHC)-peptide interaction. A 96-kDa, ER-resident glycoprotein (gp96) is being evaluated as a therapeutic agent in cancer because of its ability to associate with a vast number of cellular peptides irrespective of size or sequence. Because the antigen presentation complex is assembled in the ER and a number of ER-resident proteins are modulated by cytokines, it is important to examine the regulation of gp96 in response to immune cytokines interferon gamma (IFN-gamma), and interleukin 2 (IL-2). Defects in signaling pathway in either of the cytokines can result in suboptimal immune response. We examined the effect of the cytokines IFN-gamma and IL-2 on the induction of gp96 in different cancer cell lines and examined the induction of DNA-binding proteins that recognize gamma interferon-activating sequence (GAS), present in the promoter region of gp96. The induction of GAS binding protein correlated with the induction of STAT 1 protein, a transcriptional regulator and mediator of IFN-gamma-mediated gene expression. The use of cytokines in inducing gp96 levels may have significance in maintaining high levels of gp96 for a sustained immune response.
Y G Chen; B T Ashok; X Liu; V P S Garikapaty; A Mittelman; R K Tiwari
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Cell stress & chaperones     Volume:  8     ISSN:  1355-8145     ISO Abbreviation:  Cell Stress Chaperones     Publication Date:  2003  
Date Detail:
Created Date:  2004-02-26     Completed Date:  2004-08-12     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  9610925     Medline TA:  Cell Stress Chaperones     Country:  United States    
Other Details:
Languages:  eng     Pagination:  242-8     Citation Subset:  IM    
Department of Microbiology and Immunology and Medicine, New York Medical College, Valhalla, NY 10595, USA.
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MeSH Terms
Antigens, Neoplasm / analysis,  biosynthesis*
Cell Line, Tumor
HSP90 Heat-Shock Proteins / analysis,  metabolism
Interferon-gamma / immunology,  pharmacology*,  physiology
Interleukin-2 / immunology,  pharmacology*,  physiology
Transcriptional Activation
Reg. No./Substance:
0/Antigens, Neoplasm; 0/HSP90 Heat-Shock Proteins; 0/Interleukin-2; 0/sarcoma glycoprotein gp96 rejection antigens; 82115-62-6/Interferon-gamma

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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