RESUMO
Extracellular vesicles (EVs) are evaginations of the cytoplasmic membrane, containing nucleic acids, proteins, lipids, enzymes, and toxins. EVs participate in various bacterial physiological processes. Staphylococcus epidermidis interacts and communicates with the host skin. S. epidermidis' EVs may have an essential role in this communication mechanism, modulating the immunological environment. This work aimed to evaluate if S. epidermidis' EVs can modulate cytokine production by keratinocytes in vitro and in vivo using the imiquimod-induced psoriasis murine model. S. epidermidis' EVs were obtained from a commensal strain (ATC12228EVs) and a clinical isolated strain (983EVs). EVs from both origins induced IL-6 expression in HaCaT keratinocyte cultures; nevertheless, 983EVs promoted a higher expression of the pro-inflammatory cytokines VEGF-A, LL37, IL-8, and IL-17F than ATCC12228EVs. Moreover, in vivo imiquimod-induced psoriatic skin treated with ATCC12228EVs reduced the characteristic psoriatic skin features, such as acanthosis and cellular infiltrate, as well as VEGF-A, IL-6, KC, IL-23, IL-17F, IL-36γ, and IL-36R expression in a more efficient manner than 983EVs; however, in contrast, Foxp3 expression did not significantly change, and IL-36 receptor antagonist (IL-36Ra) was found to be increased. Our findings showed a distinctive immunological profile induction that is dependent on the clinical or commensal EV origin in a mice model of skin-like psoriasis. Characteristically, proteomics analysis showed differences in the EVs protein content, dependent on origin of the isolated EVs. Specifically, in ATCC12228EVs, we found the proteins glutamate dehydrogenase, ornithine carbamoyltransferase, arginine deiminase, carbamate kinase, catalase, superoxide dismutase, phenol-soluble ß1/ß2 modulin, and polyglycerol phosphate α-glucosyltransferase, which could be involved in the reduction of lesions in the murine imiquimod-induced psoriasis skin. Our results show that the commensal ATCC12228EVs have a greater protective/attenuating effect on the murine imiquimod-induced psoriasis by inducing IL-36Ra expression in comparison with EVs from a clinical isolate of S. epidermidis.
Assuntos
Vesículas Extracelulares/metabolismo , Psoríase/terapia , Staphylococcus epidermidis/metabolismo , Animais , Antígenos Ly/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Vesículas Extracelulares/química , Vesículas Extracelulares/transplante , Humanos , Imiquimode/toxicidade , Interleucina-1/antagonistas & inibidores , Interleucina-1/genética , Interleucina-1/metabolismo , Interleucina-17/genética , Interleucina-17/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Camundongos , Infiltração de Neutrófilos , Psoríase/induzido quimicamente , Psoríase/patologia , Pele/metabolismo , Pele/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Calcification of the ridge between the sinus of Valsalva and the tubular segments of the ascending aorta has been documented at autopsy, but no echocardiographic description has yet been published. We describe the two-dimensional echocardiographic appearances in 33 men (mean age, 69 years). Sinotubular ridge calcification manifested as a dense small echo projecting into the aortic lumen, precisely at the junction of the sinus of Valsalva and tubular aortic segments. Calcification in the aortic valve cusps, mitral annulus, basal mitral leaflets, and papillary muscles also were frequently present. This previously unknown entity must be distinguished from atheromatous aortic plaques.