engleski

Induction of cytokines, chemokines, and metalloproteinases in endothelial cells infected with hantaviruses

Hantaviruses, cause two different clinical manifestations in humans: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Human endothelial cells (ECs) together with monocytes/macrophages appear to be the main target cells susceptible to hantavirus infection and the main pathologic event is increase in vascular permeability, which is accompanied by endothelial activation, increased expression of adhesion molecules, and recruitment of inflammatory cells in the organs involved. The aim of the study is to look for the possible role of cytokines, chemokines and metalloproteinases (MMPs) in endothelial cells infected with HFRS/HPS hantaviruses. The human vein ECs (HUVEC) were infected with Hantaan (HTNV), Andes (ANDV), and Sin Nombre (SNV) viruses. The cells were incubated for 7 days at 37 °C, 5% CO2 . Uninfected cells were used as controls. Supernatants of infected and uninfected cells were collected at various time points in which we measured levels of different cytokines (IL-1beta, IL-6, IL-10, IL-12p40, GM-CSF, IFN-gamma, TNF-alpha) and chemokines (IL-8/CXCL-8, RANTES/CCL5, MCP-1/CCL2, MIP-1alpha/CCL3, MIP-1beta/CCL4) by specific ELISA tests (Pharmingen or R&D Systems, Inc., Minneapolis, MN, USA). Additionally, MMP-2 and MMP-9, as well as IL-8 were detected by RT-PCR. In HUVEC, HTNV induced continuous production of IL-6, IL-10 and IL-12p40 while SNV induced production for only three days and ANDV showed no induction. All three hantaviruses induced RANTES/CCL5 production but only SNV induced MCP-1/CCL2 production. HPS-causing viruses (SNV and ANDV) decreased production of IL-8/CXCL8. Slight increase at the gene expression level was observed for MMP-2 20 h after infection with ANDV. To our knowledge, we are the first to observe production of IL-10 and IL-12p40 in HUVEC infected with HTV. In summary, our study showed that HTV induced production of several cytokines (IL-6, IL-10 and IL-12) and chemokines (RANTES/CCL5, MCP-1/CCL2 and IL-8/CXCL8). Our results showed that HTV activate ECs to produce different cytokines/chemokines which participate in inflammatory and immune reactions in HFRS/HPS. Although the cytokine/chemokine profile was not specific for HTV, some of our findings open new questions for future research. The changes in MMPs could be expected in early phase of infection.

hantaviruses; endothelial cells; immunoreactions; cytokines; chemokines; matrix metalloproteinases

Rad je kao poster na hrvatskom jeziku, pod naslovom 'Indukcija citokina, kemokina i metaloproteinaza u endotelnim stanicama inficiranim hantavirusima' prezentiran i na skupu 74. znanstveno-stručni simpozij s međunarodnim sudjelovanjem Nove spoznaje na području infektivnih bolesti, održanom od 10.-12.04.2008., Šibenik, Hrvatska.