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  • Title: Heat shock protein (HSP72) and p38 MAPK involvement in sublethal hemorrhage (SLH)-induced tolerance.
    Author: Carter Y, Liu G, Stephens WB, Carter G, Yang J, Mendez C.
    Journal: J Surg Res; 2003 May 01; 111(1):70-7. PubMed ID: 12842450.
    Abstract:
    BACKGROUND: Our in vivo model of tolerance, sublethal hemorrhage (SLH), alters cytokine production, nuclear factor-kappaB mobilization, mitogen-activated protein (MAP) kinase activity, and makes rats tolerant to shock. Heat shock protein (HSP) protects animals from stress. This study investigated if SLH induces in vivo HSP72 expression and whether in vitro HSP72 induction by sodium arsenite (NaArs) alters intracellular signal transduction and cytokine production similar to SLH. METHODS: Sprague-Dawley rats were made tolerant by SLH (MAP = 30 mmHg for 15 min, shed blood returned) and given lipopolysaccharide (LPS; 40 mg/kg i.p.) 24 h later. Lung was harvested 1, 12, and 24 h after SLH (n = 4) and 1 h after LPS (n = 8). Other rats underwent bronchoalveolar lavage 24 h after SLH, and macrophages (mphi) were treated with LPS (10 microg/ml). The NR8383 alveolar mphi cell line was treated with 50 microM NaArsx 12 h and LPS. Reverse transcription polymerase chain reaction, Western blots, and enzyme-linked immunosorbent assay were performed for gene, MAPK, and protein expression (tumor necrosis factor [TNF], HSP, p38). RESULTS: SLH induced significantly more lung HSP72 mRNA and protein. SLH mphi had more HSP72 protein before and after LPS compared with shams. NaArs induced HSP72 mRNA and protein in NR8383 mphi, and these cells made less TNF compared with controls. NaArs significantly increased p38 activation vs control. SB203580 inhibition of p38 activity did not affect HSP72 expression, or reverse NaArs inhibition of LPS induced TNF production. CONCLUSION: SLH induces HSP72 in vivo. In vitro HSP72 induction is associated with increased p38 phosphorylation. Like SLH, mphi with induced HSP72 expression, have an attenuated TNF response. HSP72 acts independently from p38 in inducing tolerance.
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