scholarly journals Plasma Membrane Expression of Heat Shock Protein 60 In Vivo in Response to Infection

1999 ◽  
Vol 67 (8) ◽  
pp. 4191-4200 ◽  
Author(s):  
Cindy Belles ◽  
Alicia Kuhl ◽  
Rachel Nosheny ◽  
Simon R. Carding
Keyword(s):  
Plasma Membrane ◽  
T Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cell Receptor ◽  
T Cell Response ◽  
Heat Shock Protein 60 ◽  
Membrane Expression ◽  
Hsp60 Expression

ABSTRACT Heat shock protein 60 (hsp60) is constitutively expressed in the mitochondria of eukaryotic cells. However, it has been identified in other subcellular compartments in several disease states and in transformed cells, and it is an immunogenic molecule in various infectious and autoimmune diseases. To better understand the factors that influence expression of hsp60 in normal cells in vivo, we analyzed its cellular and subcellular distribution in mice infected with the intracellular bacterium Listeria monocytogenes. Western blotting of subcellular fractionated spleen cells showed that although endogenous hsp60 was restricted to the mitochondria in noninfected animals, it was associated with the plasma membrane as a result of infection. The low levels of plasma membrane-associated hsp60 seen in the livers in noninfected animals subsequently increased during infection. Plasma membrane hsp60 expression did not correlate with bacterial growth, being most evident during or after bacterial clearance and persisting at 3 weeks postinfection. Using flow cytometry, we determined that Mac-1+, T-cell receptor γδ+, and B220+ cells represented the major Hsp60+ populations in spleens of infected mice. By contrast, B220+ cells were the predominant hsp60+ population in livers of infected mice. Of the immune cells analyzed, the kinetic profile of the γδ T-cell response most closely matched that of hsp60 expression in both the spleen and liver. Collectively, these findings show that during infection hsp60 can be localized to the plasma membrane of viable cells, particularly antigen-presenting cells, providing a means by which hsp60-reactive lymphocytes seen in various infectious disease and autoimmune disorders may be generated and maintained.

scholarly journals A Deficiency in Gamma Interferon or Interleukin-10 Modulates T-Cell-Dependent Responses to Heat Shock Protein 60 from Histoplasma capsulatum

2005 ◽  
Vol 73 (4) ◽  
pp. 2129-2134 ◽  
Author(s):  
Mark Scheckelhoff ◽  
George S. Deepe
Keyword(s):  
T Cells ◽  
T Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cell Receptor ◽  
Interleukin 10 ◽  
Gamma Interferon ◽  
Heat Shock Protein 60 ◽  
Wild Type ◽  
Deficient Mice

ABSTRACT Immunization of mice with heat shock protein 60 from Histoplasma capsulatum or a polypeptide from the protein designated F3 confers protection. Vβ8.1/8.2+ T cells are critically important for the protective efficacy of this antigen. The production of interleukin-10 and gamma interferon following vaccination is essential for efficacy. In this study, we sought to determine whether the absence of either cytokine modified the repertoire of antigen-reactive T cells and whether it altered the functional properties of T cells. Mice lacking gamma interferon or interleukin-10 manifested a skewed repertoire compared to that of wild-type mice. The bias was most marked in gamma interferon-deficient mice and modestly altered in interleukin-10-deficient animals. The altered repertoire in gamma interferon-deficient mice could not be explained at the level of antigen presentation or by the absence of this population from mice. The proportion of T cells from interleukin-10-deficient mice manifesting a Th1 phenotype was greatly increased compared to that from wild-type animals. Transfer of splenocytes from gamma interferon- or interleukin-10-deficient mice immunized with heat shock protein 60 failed to confer protection in T-cell receptor α/β−/− mice. The transfer of T-cell clones that did not produce both cytokines failed to prolong survival in T-cell receptor α/β−/− mice, whereas the clones with the same features that were derived from wild-type mice did. These results indicate that the cytokine milieu influences the shape of the T-cell receptor repertoire and support the importance of gamma interferon and interleukin-10 in the efficacy of heat shock protein 60.

scholarly journals Identification and characterization of molecular interactions between mortalin/mtHsp70 and HSP60

2005 ◽  
Vol 391 (2) ◽  
pp. 185-190 ◽  
Author(s):  
Renu Wadhwa ◽  
Syuichi Takano ◽  
Kamaljit Kaur ◽  
Satoshi Aida ◽  
Tomoko Yaguchi ◽  
...  
Keyword(s):  
Heat Shock ◽  
Molecular Interactions ◽  
Heat Shock Protein 60 ◽  
Hsp60 Expression ◽  
Mitochondrial Hsp70 ◽  
Shock Proteins ◽  
First Time

Mortalin/mtHsp70 (mitochondrial Hsp70) and HSP60 (heat-shock protein 60) are heat-shock proteins that reside in multiple subcellular compartments, with mitochondria being the predominant one. In the present study, we demonstrate that the two proteins interact both in vivo and in vitro, and that the N-terminal region of mortalin is involved in these interactions. Suppression of HSP60 expression by shRNA (short hairpin RNA) plasmids caused the growth arrest of cancer cells similar to that obtained by suppression of mortalin expression by ribozymes. An overexpression of mortalin, but not of HSP60, extended the in vitro lifespan of normal fibroblasts (TIG-1). Taken together, this study for the first time delineates: (i) molecular interactions of HSP60 with mortalin; (ii) their co- and exclusive localizations in vivo; (iii) their involvement in tumorigenesis; and (iv) their functional distinction in pathways involved in senescence.

scholarly journals Protection against streptococcal cell wall-induced arthritis by pretreatment with the 65-kD mycobacterial heat shock protein.

1989 ◽  
Vol 170 (2) ◽  
pp. 449-466 ◽  
Author(s):  
M F van den Broek ◽  
E J Hogervorst ◽  
M C Van Bruggen ◽  
W Van Eden ◽  
R van der Zee ◽  
...  
Keyword(s):  
Cell Wall ◽  
T Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Delayed Type Hypersensitivity ◽  
Streptococcal Cell Wall ◽  
Amino Acid Homology ◽  
Lymphoid Cell Population ◽  
Shock Proteins

We report that streptococcal cell wall (SCW)-induced arthritis in rats, a T cell-dependent chronic, erosive polyarthritis, can be prevented by pretreatment of the rats with the mycobacterial 65-kD heat shock protein. This 65-kD protein shows extensive amino acid homology with prokaryotic and eukaryotic 65-kD heat shock proteins and is a ubiquitous bacterial common antigen. Both the clinical and histopathologic manifestations of the arthritis were prevented completely when rats were pretreated with 50 micrograms of 65-kD protein intraperitoneally at 35, 25, 15, or 5 d before administration of SCW. In such protected rats, SCW-specific T cell responses were suppressed, as compared with responses in arthritic rats. Pretreatment with 65-kD protein had no effect on the production of antibodies against SCW, on a nonspecific inflammatory reaction (zymosan-induced arthritis), or on general cellular immunity in vivo (delayed type hypersensitivity reaction to a nonrelated protein antigen). Furthermore, the protection against SCW arthritis was transferable by splenic T cells to naive recipients. Our data show that pretreatment with the 65-kD mycobacterial heat shock protein protects rats against a subsequent bacterium-induced arthritis. This protection is immunologically specific and resides in the lymphoid cell population.

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