Host's Endogenous Caveolin-1 Expression is Downregulated in the Lung During Sepsis to Promote Cytoprotection. Issue 2 (August 2018)

• Record Type: Journal Article
• Authors: Kataki, Agapi; Karagiannidis, Ioannis; Memos, Nikolaos; Koniaris, Efthymios; Antonakis, Pantelis; Papalois, Apostolos; Zografos, George C.; Konstadoulakis, Manoussos M.
• Is Part Of: Shock. Volume 50:Issue 2(2018)
• Publication Date: 2018-08
• Subjects: 14-3-3b -- caveolin-1 -- CLP model -- pAkt -- PC -- pP38 -- S100 -- sepsis -- − -- negative stained -- + -- positive stained -- 7AAD -- 7-aminoactinomycin D protein -- APC -- activated protein C -- CLP -- cecal ligation and puncture -- EPCR -- endothelial protein C receptor -- FITC -- fluorescein isothiocyanate -- MAPK -- mitogen-activated protein kinase -- MFI -- mean fluorescent intensity -- pAkt -- phospho-Akt -- PAR-1 -- protease-activated receptor-1 -- PBS -- phosphate-buffered saline -- PC -- human protein C concentrate -- PE -- phycoerythrin -- pP38 -- phosphorylated-P38 -- rhAPC -- recombinant human-activated protein C -- SEM value -- standard error of the mean -- Treg -- regulatory T cell; Shock -- Periodicals; Shock -- Periodicals; Choc (Pathologie) -- Périodiques; Shock; Periodicals; 616.0475
• DOI: 10.1097/SHK.0000000000001005
• Languages: English
• ISSNs: 1073-2322

Abstract

Abstract : 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, 12, 24, 36, and 48 h after 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. After 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 and 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), whereas 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-dependent apoptosis and EPCR-PAR-1-dependent protective signaling.