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Host’s Endogenous Caveolin-1 Expression is Downregulated in the Lung During Sepsis to Promote Cytoprotection.

Host’s Endogenous Caveolin-1 Expression is Downregulated in the Lung During Sepsis to Promote Cytoprotection.
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Kataki A, Karagiannidis I, Memos N, Koniaris E, Antonakis P, Papalois A, Zografos GC, Konstadoulakis MM,


Kataki A, Karagiannidis I, Memos N, Koniaris E, Antonakis P, Papalois A, Zografos GC, Konstadoulakis MM, (click to view)

Kataki A, Karagiannidis I, Memos N, Koniaris E, Antonakis P, Papalois A, Zografos GC, Konstadoulakis MM,

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Shock (Augusta, Ga.) 2017 09 27() doi 10.1097/SHK.0000000000001005
Abstract

The present study focuses on the profile of ‘endogeneous’ caveolin-1 protein in septic lung (CLP model).Caveolin-1, CD25, pP38, pAkt and 14-3-3b protein expression profiles were studied using flow cytometry and immunohistochemistry 6 h, 12 h, 24 h, 36 h and 48 h following sepsis induction. Cell viability was determined by 7-AAD staining and fibrosis by Masson trichrome stain. The effect of protein C zymogen concentrate (PC) on caveolin-1 expression was also investigated given that PC, once dissociated from caveolin-1, elicits a PAR-1-mediated protective signaling by forming a complex with endothelial protein C receptor (EPCR).CLP treatment increased lung inflammation and cell apoptosis. Fibrosis was apparent in vessels and alveoli. Caveolin-1+ cells presented reduced protein expression, especially 12 h post-CLP (p = 0.002). Immunohistochemistry revealed caveolin-1 positive expression mainly in regions with strong inflammatory reaction. Early induction of pP38+ cell population (p = 0.014) and gradual increase of CD25+ cells were also observed. Alternations in 14-3-3b expression related to apoptosis were apparent and accompanied by increased AKT phosphorylation activity late during sepsis progression.Following PC administration, cell apoptosis was reduced (p = 0.004) and both the percentile and expression intensity of caveolin-1 positive cells were compromised (p = 0.009, p = 0.027 respectively). 14-3-3b, CD25 and pP38 protein expression were decreased (p = 0.014, p = 0.004 and p = 0.007, respectively) while pAkt expression was induced (p = 0.032).The observed decline of endogenous caveolin-1 protein expression during sepsis implies its involvement in host’s cytoprotective reaction either directly, by controlling caveolae population to decrease bacterial burden, or indirectly via regulating 14-3-3b depended apoptosis and EPCR-PAR-1 dependent protective signaling.

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