naa a22 4500 510745792 CHVBK 20180411083045.0 cr unu---uuuuu 180411e20130101xx s 000 0 eng 10.1007/s12192-012-0356-0 doi (NATIONALLICENCE)springer-10.1007/s12192-012-0356-0 Extracellular HSP27 acts as a signaling molecule to activate NF-κB in macrophages [Elektronische Daten] [Samira Salari, Tara Seibert, Yong-Xiang Chen, Tieqiang Hu, Chunhua Shi, Xiaoling Zhao, Charles Cuerrier, Joshua Raizman, Edward O'Brien] Heat shock protein 27 (HSP27) shows attenuated expression in human coronary arteries as the extent of atherosclerosis progresses. In mice, overexpression of HSP27 reduces atherogenesis, yet the precise mechanism(s) are incompletely understood. Inflammation plays a central role in atherogenesis, and of particular interest is the balance of pro- and anti-inflammatory factors produced by macrophages. As nuclear factor-kappa B (NF-κB) is a key immune signaling modulator in atherogenesis, and macrophages are known to secrete HSP27, we sought to determine if recombinant HSP27 (rHSP27) alters NF-κB signaling in macrophages. Treatment of THP-1 macrophages with rHSP27 resulted in the degradation of an inhibitor of NF-κB, IκBα, nuclear translocation of the NF-κB p65 subunit, and increased NF-κB transcriptional activity. Treatment of THP-1 macrophages with rHSP27 yielded increased expression of a variety of genes, including the pro-inflammatory factors, IL-1β, and TNF-α. However, rHSP27 also increased the expression of the anti-inflammatory factors IL-10 and GM-CSF both at the mRNA and protein levels. Our study suggests that in macrophages, activation of NF-κB signaling by rHSP27 is associated with upregulated expression and secretion of key pro- and anti-inflammatory cytokines. Moreover, we surmise that it is the balance in expression of these mediators and antagonists of inflammation, and hence atherogenesis, that yields a favorable net effect of HSP27 on the vessel wall. Cell Stress Society International, 2012 Heat shock protein 27 (HSP27) nationallicence Macrophage nationallicence Nuclear factor-kappa B (NF-κB) signaling nationallicence Atherosclerosis nationallicence Salari Samira University of Ottawa Heart Institute, Ottawa, ON, Canada aut Seibert Tara University of Ottawa Heart Institute, Ottawa, ON, Canada aut Chen Yong-Xiang University of Ottawa Heart Institute, Ottawa, ON, Canada aut Hu Tieqiang University of Ottawa Heart Institute, Ottawa, ON, Canada aut Shi Chunhua University of Ottawa Heart Institute, Ottawa, ON, Canada aut Zhao Xiaoling University of Ottawa Heart Institute, Ottawa, ON, Canada aut Cuerrier Charles University of Ottawa Heart Institute, Ottawa, ON, Canada aut Raizman Joshua University of Ottawa Heart Institute, Ottawa, ON, Canada aut O'Brien Edward University of Ottawa Heart Institute, Ottawa, ON, Canada aut Cell Stress and Chaperones Springer Netherlands 18/1(2013-01-01), 53-63 1355-8145 18:1<53 2013 18 12192 https://doi.org/10.1007/s12192-012-0356-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12192-012-0356-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Salari Samira University of Ottawa Heart Institute, Ottawa, ON, Canada aut NATIONALLICENCE 700 1- Seibert Tara University of Ottawa Heart Institute, Ottawa, ON, Canada aut NATIONALLICENCE 700 1- Chen Yong-Xiang University of Ottawa Heart Institute, Ottawa, ON, Canada aut NATIONALLICENCE 700 1- Hu Tieqiang University of Ottawa Heart Institute, Ottawa, ON, Canada aut NATIONALLICENCE 700 1- Shi Chunhua University of Ottawa Heart Institute, Ottawa, ON, Canada aut NATIONALLICENCE 700 1- Zhao Xiaoling University of Ottawa Heart Institute, Ottawa, ON, Canada aut NATIONALLICENCE 700 1- Cuerrier Charles University of Ottawa Heart Institute, Ottawa, ON, Canada aut NATIONALLICENCE 700 1- Raizman Joshua University of Ottawa Heart Institute, Ottawa, ON, Canada aut NATIONALLICENCE 700 1- O'Brien Edward University of Ottawa Heart Institute, Ottawa, ON, Canada aut NATIONALLICENCE 773 0- Cell Stress and Chaperones Springer Netherlands 18/1(2013-01-01), 53-63 1355-8145 18:1<53 2013 18 12192 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer