Lowered temperature set point for activation of the cellular stress response in T-lymphocytes.
The induction of heat shock protein gene expression in response to stress is critical for the ability of organisms to cope with and survive exposure to these stresses. However, most studies on HSF1-mediated induction of hsp70 gene expression have utilized immortalized cell lines and temperatures above the physiologically relevant range. For these reasons much less is known about the heat shock response as it occurs in mammalian cells within tissues in the intact organism. To gain insight into this area we determined the temperature thresholds for activation of HSF1 DNA binding in different mouse tissues. We have found that HSF1 DNA binding activity and hsp70 synthesis are induced in spleen cells at significantly lower temperatures relative to cells of other tissues, with a temperature threshold for activation (39 degrees C) that is within the physiological range for fever. Furthermore, we found that the lowered temperature set point for induction of the stress response in spleen is specific to T-lymphocytes residing within this tissue and is not exhibited by B-lymphocytes. This lowered threshold is also observed in T-lymphocytes isolated from lymph nodes, suggesting that it is a general property of T-lymphocytes, and is seen in different mouse strains. Fever is an early event in the immune response to infection, and thus activation of the cellular stress response in T-lymphocytes by fever temperatures could serve as a way to give these cells enough time to express hsps in anticipation of their function in the coming immune response. The induced hsps likely protect these cells from the stressful conditions that can exist during the immune response, for example increasing their protection against stress-induced apoptosis.
Gothard
Lisa Q
LQ
Department of Molecular and Cellular Biochemistry, University of Kentucky, Chandler Medical Center, Lexington, Kentucky 40536-0294, USA.
Ruffner
Marvin E
ME
Woodward
Jerold G
JG
Park-Sarge
Ok-Kyong
OK
Sarge
Kevin D
KD
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D005334:Fever; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology; D013312:Stress, Physiological; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology*; D013696:Temperature; D013997:Time Factors; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors