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Toxoplasma gondii serine-protease inhibitor-1: A new adjuvant candidate for asthma therapy

Soto, Ariadna S ; Fenoy, Ignacio M ; Sanchez, Vanesa R ; March, Florencia ; Perrone Sibilia, Matías D ; Aldirico, María de Los Angeles ; Picchio, Mariano S ; Arcon, Nadia ; Acosta, Patricio L ; Polack, Fernando P ; Martin, Valentina ; Goldman, Alejandra Kato, Takuma

PloS one, 2017-10, Vol.12 (10), p.e0187002-e0187002 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Toxoplasma gondii serine-protease inhibitor-1: A new adjuvant candidate for asthma therapy
Autor: Soto, Ariadna S ; Fenoy, Ignacio M ; Sanchez, Vanesa R ; March, Florencia ; Perrone Sibilia, Matías D ; Aldirico, María de Los Angeles ; Picchio, Mariano S ; Arcon, Nadia ; Acosta, Patricio L ; Polack, Fernando P ; Martin, Valentina ; Goldman, Alejandra
Kato, Takuma
Assuntos: Airway management ; Allergens ; Allergens - immunology ; Allergies ; Alum ; Aluminum sulfate ; Alveoli ; Analysis ; Animals ; Antiasthmatic agents ; Antibodies, Protozoan - blood ; Antibodies, Protozoan - immunology ; Antibody Specificity ; Antigens ; Asthma ; Asthma - blood ; Asthma - drug therapy ; Asthma - immunology ; Atopy ; Biology and Life Sciences ; Bronchus ; Cell proliferation ; Cell Proliferation - drug effects ; Complications and side effects ; Cytokines - biosynthesis ; Dosage and administration ; Drug Interactions ; Drug therapy ; Eosinophilia ; Forkhead Transcription Factors - metabolism ; Foxp3 protein ; Genetic aspects ; Health aspects ; Immunoglobulin E ; Immunomodulation ; Immunotherapy ; Infiltration ; Inflammation ; Interferon ; Interleukin 10 ; Interleukin 4 ; Interleukin 5 ; Lungs ; Lymph nodes ; Lymphocytes ; Lymphocytes T ; Medicine and Health Sciences ; Mice ; Mice, Inbred BALB C ; Mucus ; Neutrophils ; Ovalbumin ; Ovalbumin - therapeutic use ; Pathogenesis ; Physiological aspects ; Protease ; Protease inhibitors ; Proteases ; Proteinase inhibitors ; Recombinant Proteins - pharmacology ; Recombinant Proteins - therapeutic use ; Research and Analysis Methods ; Respiratory tract ; Rodents ; Secondary aerosols ; Serine ; Serine proteinase ; Serine Proteinase Inhibitors - pharmacology ; Serine Proteinase Inhibitors - therapeutic use ; T-Lymphocytes, Regulatory - cytology ; T-Lymphocytes, Regulatory - drug effects ; T-Lymphocytes, Regulatory - immunology ; T-Lymphocytes, Regulatory - metabolism ; Thorax ; Toxoplasma ; Toxoplasma gondii ; γ-Interferon
É parte de: PloS one, 2017-10, Vol.12 (10), p.e0187002-e0187002
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Competing Interests: The authors have declared that no competing interests exist.
Descrição: Serine-proteases are important players in the pathogenesis of asthma, promoting inflammation and tissue remodeling. It's also known that many serine protease inhibitors display immunomodulatory properties. TgPI-1 is a Toxoplasma gondii protein that exhibits broad spectrum inhibitory activity against serine proteases. In view of the increased prevalence of atopic disorders and the need to develop new treatment strategies we sought to investigate the potential of TgPI-1 for treating respiratory allergies. For this purpose, we developed a therapeutic experimental model. BALB/c mice were rendered allergic by intraperitoneal ovalbumin-alum sensitization and airway-challenged. Once the asthmatic phenotype was achieved, mice were intranasally treated with rTgPI-1 alone or with a mixture of rTgPI-1 and ovalbumin (OVA). A week later mice were given a secondary aerosol challenge. Treatment with rTgPI-1 alone or co-administered with OVA diminished bronchoalveolar eosinophilia, mucus production and peribronchial lung infiltration. This effect was accompanied by a lung resistance reduction of 26.3% and 50.3% respectively. Both treatments resulted in the production of lower levels of IL-4, IL-5, IFN-γ and regulatory IL-10 by thoracic lymph node cells stimulated with OVA. Interestingly, significant decreases in OVA specific IgE and T cell proliferation, and increases in FoxP3+ T cells at local and systemic levels were only detected when the inhibitor was administered along with OVA. These results show that both rTgPI-1 treatments reduced asthma hallmarks. However, co-administration of the inhibitor with the allergen was more effective. Hence, rTgPI-1 emerges as a novel adjuvant candidate for asthma treatment.
Editor: United States: Public Library of Science
Idioma: Inglês

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Toxoplasma gondii serine-protease inhibitor-1: A new adjuvant candidate for asthma therapy

Soto, Ariadna S ; Fenoy, Ignacio M ; Sanchez, Vanesa R ; March, Florencia ; Perrone Sibilia, Matías D ; Aldirico, María de Los Angeles ; Picchio, Mariano S ; Arcon, Nadia ; Acosta, Patricio L ; Polack, Fernando P ; Martin, Valentina ; Goldman, Alejandra Kato, Takuma

United States: Public Library of Science

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