Heat shock treatment suppresses angiotensin II-induced activation of NF-kappaB pathway and heart inflammation: a role for IKK depletion by heat shock?
Heat shock (HS) proteins (Hsps) function in tissue protection through their chaperone activity and by interacting with cell signaling pathways to suppress apoptosis. Here, we investigated the effect of HS treatment on the nuclear factor (NF)-kappaB signaling pathway in the angiotensin II (ANG II) model of inflammation. Male Sprague-Dawley rats were divided into sham and HS-, ANG II-, and HS + ANG II-treated groups. HS treatment was administered 24 h before the initiation of ANG II infusion. HS treatment (42 degrees C for 15 min) decreased 7-day ANG II-induced hypertension from 191 +/- 4 to 147 +/- 3 mmHg (P < 0.01). Histological staining of hearts showed that HS treatment reduced ANG II-induced leukocyte infiltration, perivascular and interstitial inflammation, and fibrosis. Heart NF-kappaB nuclear translocation and activity, examined by Western blot analysis and electrophoretic mobility shift assay, was suppressed by HS treatment. HS treatment depleted IkappaB kinase-alpha (IKK-alpha) and phosphorylated IKK-alpha and suppressed the depletion of IkappaB-alpha and the accumulation of phosphorylated IkappaB-alpha. HS treatment blocked ANG II induced expression of IL-6 and ICAM-1 in the heart. ANG II and HS treatment induced high-level expression of Hsp27 and Hsp70 and their phosphorylation. Phosphorylated isoforms of Hsp27 and Hsp70 may play an important role in protecting the heart against ANG II-induced inflammation.
Chen
Yu
Y
Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 1X5.
Arrigo
André-Patrick
AP
Currie
R William
RW
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006358:Hot Temperature; D051550:I-kappa B Kinase; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009205:Myocarditis / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012769:Shock / Q000209:etiology* / Q000517:prevention & control*
D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D015850:Interleukin-6; D016328:NF-kappa B; D000804:Angiotensin II; D018799:Intercellular Adhesion Molecule-1; D017346:Protein Serine-Threonine Kinases; D051550:I-kappa B Kinase