engleski

Early activation mechanisms in lung fibroblasts infected with Hantaviruses

Lung disorders dominate in HPS, but also are found in HFRS. Sequestration of peripheral blood monocytes within the lungs is characteristic of a number of acute and chronic lung disorders. Additionally, alveolar macrophages are derived predominantly from different peripheral blood monocytes and the presence of increased numbers of activated macrophages can lead to tissue injury through the excessive elaboration of inflammatory cytokines. Fibroblasts are important participants in the orchestration of acute and chronic inflammation and fibrosis. The production of inflammatory cytokines from lung fibroblasts may have a role in the cell recruitment from the vascular compartment to the lung interstitium. Our previous results indicated that lung fibroblasts infected with hantaviruses may produce certain inflammatory cytokines and chemokines. The aim of this study was to investigate the role of some of the cytokines that are produced in the early phase of hantaviral infections. Additionally, we wanted to characterize the early expression profile of the Rel / NFkB / IkB family, genes responsive to NFkB signaling, and other genes involved in the NFkB signal transduction pathway. For that purpose, we used Focused Gene Expression cDNA Array Analysis (GEArrays, SuperArray Bioscience, Frederick, MD, USA) to compare expression profiles of genes in RNA samples from MRC-5 cells (human lung fibroblasts) after six hours of infection with Hantaan virus or Andes virus. Two different GEArrayTM were used: GEArray Q series Human Common Cytokine Gene Array and GEArray Q series Human NFkB signaling Pathway Gene Array. Selected genes identified by GEArray analysis will be also analyzed by quantitative real-time PCR to verify transcriptional responses. Hantaan virus increased expression only of interleukin-6. Both viruses decreased gene-expression of bone morphogenetic protein 2 (BMP-2). Andes virus also decreased expression of hepatocyte growth factor (HGF) and transforming growth factor  1 (TGF- 1), while increased gene expression of colony stimulating factor 1 (CSF-1) and fibroblast growth factor 11 (FGF-11). Both viruses increased gene expression for the members of Rel/NFkB/IkB family (nuclear factor related to kappa B binding protein-NFRKB) ; NFkB responsive genes (E-selectin), transcription factors (early growth response 1-EGR-1) and adaptor proteins (TNF receptor-associated factor-TRAF-1), while Hantaan virus decreased activating transcription factor 2 (ATF-2). Further investigation is necessary to rule out whether some differences among the cytokine production and NFkB signal transduction pathway in the early and late stage of lung fibroblasts infection with hantaviruses may provide some explanation about pulmonary disorders caused by HFRS- and especially HPS-causing viruses.

Hantaviruses; lung fibroblasts; gene expression

Rad je kao poster prezentiran i na skupovima: Godišnji sastanak Hrvatskog imunološkog društva, održanom od 08.-10.10.2004., Opatija, Hrvatska ; uz domacu recenziju objavljen u Knjizi sazetaka, str- 26-26 ; 11th International Congress of Mycology Microbes in a Changing World (IUMS 2005), održanom od 23.-28.07.2005., San Francisco, Kalifornija, SAD ; objavljen uz međunarodnu recenziju u Knjizi sažetaka ; ISBN 1-555-81-354-2.