Publications (42) View all
-
Article: Antitumor effect of SLPI on mammary but not colon tumor growth.
[show abstract] [hide abstract]
ABSTRACT: Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor that was related to cancer development and metastasis dissemination on several types of tumors. However, it is not known the effect of SLPI on mammary and colon tumors. The aim of this study was to examine the effect of SLPI on mammary and colon tumor growth. The effect of SLPI was tested on in vitro cell apoptosis and in vivo tumor growth experiments. SLPI over-expressing human and murine mammary and colon tumor cells were generated by gene transfection. The administration of murine mammary tumor cells over-expressing high levels of SLPI did not develop tumors in mice. On the contrary, the administration of murine colon tumor cells over-expressing SLPI, developed faster tumors than control cells. Intratumoral, but not intraperitoneal administration of SLPI, delayed the growth of tumors and increased the survival of mammary but not colon tumor bearing mice. In vitro culture of mammary tumor cell lines treated with SLPI, and SLPI producer clones were more prone to apoptosis than control cells, mainly under serum deprivation culture conditions. Herein we demonstrated that SLPI induces the apoptosis of mammary tumor cells in vitro and decreases the mammary but not colon tumor growth in vivo. Therefore, SLPI may be a new potential therapeutic tool for certain tumors, such as mammary tumors. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.Journal of Cellular Physiology 07/2012; · 3.87 Impact Factor -
Article: Inflammatory mediators in exhaled breath condensate of healthy donors and exacerbated COPD patients.
[show abstract] [hide abstract]
ABSTRACT: Samples of exhaled breath condensate (EBC) provide a convenient and non-invasive method to study inflammation in lung diseases. The aim of the present study was to evaluate and compare the inflammatory protein mediator levels in EBC from healthy donors (HD) and from patients with exacerbation of chronic obstructive pulmonary disease (COPD) using an EBC collection device with and without a coating of albumin as a carrier. We studied 13 HD and 26 patients with exacerbation of COPD. The concentrations of myeloperoxidase (MPO), IFNγ and secretory leukocyte protease inhibitor (SLPI) in EBC were measured by immunoassays. The EBC samples from HD and COPD patients showed higher concentrations of MPO when samples were recovered with an albumin-coated device. Furthermore, levels of MPO in COPD patients were significantly higher than in HD. An inverse correlation was observed between MPO and spirometric parameters (FVC and FEV1). Almost all samples collected with the albumin-coated device showed higher amounts of IFNγ and SLPI than those collected with the uncoated device. The levels of SLPI in COPD patients were significantly higher than in HD. A direct correlation was observed between FVC% predicted and SLPI. We concluded that coating the collection device with albumin increased the sensitivity of the technique, at least for measurements of MPO, SLPI and IFNγ. Furthermore, the higher levels of MPO and SLPI and lower levels of IFNγ in EBC from COPD patients could reflect the immunological status and the response of lung parenchyma to treatment during the exacerbation of the illness.Cytokine 03/2012; 58(3):361-7. · 3.02 Impact Factor -
Article: Immunotherapy with SLPI over-expressing mammary tumor cells decreases tumor growth.
[show abstract] [hide abstract]
ABSTRACT: We have demonstrated previously that the inoculation of murine mammary tumor cells genetically modified to express high levels of secretory leukocyte protease inhibitor (2C1) do not develop tumors in immunocompetent mice and these cells are more prone to apoptosis than control cells. The aim of the present study was to evaluate the role of the adaptive immune response in the lack of tumor growth of 2C1 cells and the possibility of using these cells for immunotherapy. The s.c. administration of mock transfected F3II cells induces tumor in BALB/c and Nude mice. However, the inoculation of 2C1 cells develops tumor in Nude but not in BALB/c mice. The inoculation of mock transfected F3II cells to 2C1 immunized BALB/c mice by repeated administration of 2C1 cells (once a week for 3 weeks) developed significantly smaller tumors than those observed in non-immunized mice. Remarkably, survival of tumor-bearing immunized mice was higher than non-immunized animals. Herein, we demonstrate that an immunotherapy with SLPI over-expressing non-irradiated tumor cells which do not develop tumor in immunocompetent mice, partially restrain the tumor growth induced by F3II cells and increase the survival of the mice.Cancer Immunology and Immunotherapy 06/2011; 60(6):895-900. · 3.70 Impact Factor -
Article: Micro-encapsulated secretory leukocyte protease inhibitor decreases cell-mediated immune response in autoimmune orchitis.
[show abstract] [hide abstract]
ABSTRACT: We previously reported that recombinant human Secretory Leukocyte Protease Inhibitor (SLPI) inhibits mitogen-induced proliferation of human peripheral blood mononuclear cells. To determine the relevance of this effect in vivo, we investigated the immuno-regulatory role of SLPI in an experimental autoimmune orchitis (EAO) model. In order to increase SLPI half life, poly-ε-caprolactone microspheres containing SLPI were prepared and used for in vitro and in vivo experiments. Multifocal orchitis was induced in Sprague-Dawley adult rats by active immunization with testis homogenate and adjuvants. Microspheres containing SLPI (SLPI group) or vehicle (control group) were administered s.c. to rats during or after the immunization period. In vitro SLPI-release microspheres inhibited rat lymphocyte proliferation and retained trypsin inhibitory activity. A significant decrease in EAO incidence was observed in the SLPI group (37.5%) versus the control group (93%). Also, SLPI treatment significantly reduced severity of the disease (mean EAO score: control, 6.33±0.81; SLPI, 2.72±1.05). In vivo delayed-type hypersensitivity and ex vivo proliferative response to testicular antigens were reduced by SLPI treatment compared to control group (p<0.05). Our results highlight the in vivo immunosuppressive effect of released SLPI from microspheres which suggests its feasible therapeutic use.Life sciences 05/2011; 89(3-4):100-6. · 2.56 Impact Factor -
Article: Secretory leukocyte protease inhibitor: a secreted pattern recognition receptor for mycobacteria.
[show abstract] [hide abstract]
ABSTRACT: Human secretory leukocyte protease inhibitor (SLPI) displays bactericidal activity against pathogens such as Escherichia coli and Streptococcus. Furthermore, it has been reported that murine SLPI shows potent antimycobacterial activity. The aim of the present study was to investigate whether human recombinant SLPI not only kills mycobacteria but also acts as a pattern recognition receptor for the host immune system. For the in vivo experiment, BALB/c mice were infected by intranasal instillation with Mycobacterium bovis BCG and viable BCG load in lung homogenates was later determined. For the in vitro experiments, SLPI was incubated overnight with a suspension of M. bovis BCG or the virulent strain Mycobacterium tuberculosis H37Rv, and the percentage survival as well as the binding of SLPI to mycobacteria was determined. Furthermore, bacteria phagocytosis was also determined by flow cytometry. Intranasal SLPI treatment decreased the number of colony-forming units recovered from lung homogenates, indicating that SLPI interfered with M. bovis BCG infection. Moreover, SLPI decreased the viability of both M. bovis BCG and H37Rv. We demonstrated that SLPI attached to the surface of the mycobacteria by binding to pathogen-associated molecular pattern mannan-capped lipoarabinomannans and phosphatidylinositol mannoside. Furthermore, we found that in the sputum of patients with tuberculosis, mycobacteria were coated with endogenous SLPI. Finally, we showed that phagocytosis of SLPI-coated mycobacteria was faster than that of uncoated bacteria. The present results demonstrate for the first time that human SLPI kills mycobacteria and is a new pattern recognition receptor for them.American Journal of Respiratory and Critical Care Medicine 12/2008; 179(3):247-53. · 11.08 Impact Factor
