Institute of Immunology Zagreb

Zagreb, Croatia

Institute of Immunology Zagreb

Zagreb, Croatia
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Santak G.,County Hospital Pozega | Santak M.,Institute of Immunology Zagreb | Forcic D.,Institute of Immunology Zagreb
Biomedicine and Pharmacotherapy | Year: 2013

Native human interferon-α (nHuIFN-α) has a stronger reductive effect on procollagen type I mRNA expression than recombinant human interferon-α (rHuIFN-α). It is partially due to the additive activity of interleukin-1β (IL-1β), which is present in small concentrations in nHuIFN-α. Here, we show that the reductive effect is also the result of the endogenous cytokines induced by the activity of nHuIFN-α. In the culture of MRC5 fibroblasts, we have further found that nHuIFN-α induces endogenous interferons in higher amounts than rHuIFN-α, measured with PCR. That is more pronounced when interferon-γ (IFN-γ) is measured. This result puts a new light on IFN-γ activity in the nHuIFN-α treatment because its role was neglected due to the loss of its activity during the nHuIFN-α preparation process. The findings lead to the conclusion that endogenous cytokines play a significant role in the nHuIFN-α -mediated reduction of procollagen type I mRNA and are therefore an important factor in potential therapeutic usage. © 2013 Elsevier Masson SAS.


Santak G.,County Hospital Pozega | Santak M.,Institute of Immunology Zagreb | Forcic D.,Institute of Immunology Zagreb
Cytokine | Year: 2013

Platelet-derived growth factor (PDGF) is a potent mediator of fibroblast proliferation and chemotaxis. Also it has been reported as a strong suppressor of interferon (IFN) expression. IFN-α has opposite effect on fibroblast function and IFN induction. Here is our early report on the effect of low concentration of PDGF-AB alone or in combination with IFN-α on IFN mRNA production in MRC5 fibroblasts. MRC5 cells incubated with IFN-α or PDGF-AB, alone or in combination, produced significant induction of IFN-α, -β and -γ mRNA in comparison with untreated cells. The induction was dose-dependent, with higher effect in cells treated with lower concentrations of PDGF-AB. Also, low concentration of PDGF-AB showed synergism with IFN-α in IFN-β and -γ induction. Results presented here open new possibilities in multi-cytokine therapy and expand previous results on PDGF activity. © 2013 Elsevier Ltd.


Santak G.,County Hospital Pozega | Santak M.,Institute of Immunology Zagreb | Forcic D.,Institute of Immunology Zagreb
Anticancer Research | Year: 2013

Background: In the present work, we compared the antitumor effects of native human interferon-α (IFN-α) (nHuIFN-α) and recombinant human IFN-α (rHuIFN-α) on human lung adenocarcinoma A549 cells. Materials and Methods: The antitumor activity was determined by measuring cell viability and apoptosis, while the abundance of mRNA, measured by polymerase chain reaction (PCR), determined the potential role of p21 and survivin in antitumor activity of nHuIFN-α. Results: The results show that nHuIFN-α significantly reduced A549 cell viability, compared to rHuIFN-α. The most potent effect of nHuIFN-α was also observed when apoptosis was measured. A549 cells treated with nHuIFN-α expressed a significantly higher amount of p21 mRNA, while the amount of survivin mRNA was significantly reduced. Conclusion: Considering both the anti-proliferative and anti-apoptotic effects of each IFN-α, we conclude that further elucidation of the mechanisms of the antitumor activity of nHuIFN-α will help in producing more effective and less toxic therapeutic protocols and preparations.


Bendelja K.,Institute of Immunology Zagreb | Rabatic S.,Institute of Immunology Zagreb
Periodicum Biologorum | Year: 2012

The control and prevention of infectious diseases through immunization is one of the greatest achievements of modern medicine since Edward Jenner pioneered smallpox vaccination. However, future challenges in improving the efficacy of existing vaccines, development of new prophylactic vaccines for infectious diseases and therapeutic immunization for noninfectious diseases require extensive work to reveal key components of the molecular immune mechanism involved. Successful activation of innate immune response is a prerequisite for successful immunization and activation of adaptive immunity. Innate immune system comprises numerous evolutionary conserved pattern-recognition receptors (PRRs) that bind structural components shared by many pathogens. Upon binding the ligand, cascade reaction results in de novo gene expression required for immediate immune response by innate immunity and the activation of specific immune response mediated by the humoral and cellular mediators. Appropriate selection of specific pattern-recognition receptor ligands (adjuvants) enables formulation of the next generation vaccines, with controlled minimal adverse symptoms and efficient adaptive immunity development.

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