Abstract
Using LPS mediated-endotoxemia BalB/C mice, the role of heat shock factor 1 (HSF1) in heat shock response (HSR) was observed. HSR was performed with 42 °C for 15 min, and recovery for 24 h at room temperature. Endotoxemia model in mouse was achieved by intra-peritoneal injection of LPS at 14 or 15 mg/kg. Lung injury and expression of inflammatory mediators were evaluated with myeloperoxidase (MPO) and maleic dialdehyde (MDA) in heart and lung, RT-PCR, hemotoxylin-eosin (HE) staining and mortality. The data showed that the survival rate was higher in HSR+LPS (HSF1+/+) group (7/15) than that in LPS (HSF1+/+) group (0/15), LPS (HSF1-/-) group (0/14) or HSR+LPS (HSF1-/-) group (0/14) within 72 h after injection of LPS at 15 mg/kg. Similarly, the survival rate was also higher in LPS (HSF1+/+) group (5/15) than that in LPS (HSF1-/-) group (0/13) or HSR+LPS (HSF1-/-) group (0/13) within 72 h after injection of LPS at 14 mg/kg. HSR significantly suppressed production of MPO and MDA induced by LPS in lung and heart in HSF1+/+ mice, but had no such effects in HSF1-/-mice after 12 h treatment with 14 mg/kg LPS. The inflammatory mediators, including SOCS3, MCSF, GCSF, IL-1β, IL-6, CCL-2 and IL-15 were up-regulated both in HSF1+/+ and HSF1-/-mice after 12 h treatment with LPS at 14 mg/kg, and HSR repressed LPS-induced up-regulation of SOCS3, MCSF, GCSF, IL-15, IL-6 and of CCL-2 in HSF1+/+ mice, but not in HSF1-/-mice. HE staining indicated that LPS at 14 mg/kg could mediate significant morphological changes, including necrosis, intravascular coagulation and leukocytes aggregation, and adherence in lung, liver and kidney in HSF1+/+and HSF1-/-mice. The morphological changes in these organs were attenuated with HSR in HSF1+/+mice, but exacerbated in HSF1-/-mice. Those results suggested that HSF1 knock out could significantly block the protection of HSR against LPS mediated-endotoxemia in Ba1B/C mice.
Original language | English (US) |
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Pages (from-to) | 424-430 |
Number of pages | 7 |
Journal | Progress in Biochemistry and Biophysics |
Volume | 35 |
Issue number | 4 |
State | Published - Apr 2008 |
Externally published | Yes |
Keywords
- Endotoxemia
- Gene knock out
- Heat shock factor 1 (HSF1)
- Heat shock response (HSR)
- Inflammatory mediators
ASJC Scopus subject areas
- Biophysics
- Biochemistry