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Agaphelin modulates the activation of human bronchial epithelial cells induced by lipopolysaccharide and IL-4
Affiliation:1. Institute of Health Sciences, Department of Clinical Medicine, Laboratory of Experimental Immunopharmacology, Federal University of Triângulo Mineiro, Uberaba, MG, 38025-350, Brazil;2. Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA;3. Laboratory of Immunology and Infectious Diseases, Triângulo Mineiro Federal University, Uberaba, Brazil;1. Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil;2. Núcleo Multidisciplinar de Pesquisa UFRJ – Xerém em Biologia (NUMPEX-BIO), Campus Duque de Caxias Professor Geraldo Cidade – Universidade Federal do Rio de Janeiro, Duque de Caxias, Rio de Janeiro, Brazil;3. Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Brazil;4. Núcleo de Doenças Infecciosas/ Núcleo de Biotecnologia- Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil;5. Laboratório de Imunopatologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Brazil;6. Faculdade de Medicina, Centro de Pesquisa em Tuberculose, Universidade Federal do Rio de Janeiro, Brazil;7. Instituto de Veterinária, Universidade Federal Rural do Rio de Janeiro, Seropédica, RJ, Brazil;1. Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, United States;2. Molecular and Cellular Biology Program, Ohio University, United States;3. Biomedical Engineering Program, Russ College of Engineering and Technology, Ohio University, United States;4. The Diabetes Institute at Ohio University, United States;1. Singapore Immunology Network (SIgN), A*STAR, Singapore;2. Department of Microbiology and Immunology, National University of Singapore (NUS), Singapore, Singapore;1. Medicina Molecular y Traslacional, Centro de Investigación en Ciencias de la Salud y Biomedicina, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, Mexico;2. Departamento de Cardiología, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, Mexico;1. Área Inmunología, DEPBIO/IQB - Facultad de Química/Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay;2. Integrative Parasitology, Center for Infectious Diseases, Heidelberg University, Heidelberg, Germany;1. Department of Medical Cell Biology, Institute for Anatomy and Cell Biology, Medical Faculty, Philipps-University of Marburg, Robert-Koch-Str. 8, 35037, Marburg, Germany;2. Section on Molecular Neuroscience, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health Intramural Research Program, Bethesda, 20814, Maryland, USA
Abstract:Sand fly saliva presents molecules with potential to development of compounds for treatment of inflammatory diseases. Agaphelin, isolated from the saliva of the mosquito Anopheles gambiae, demonstrates anti-inflammatory properties such as neutrophils chemotaxis inhibition. Here, we extend these results and evaluated the role of agaphelin (0.1−100 nM) in an in vitro model consisting in the activation of human bronchial epithelial cells (BEAS-2B) by IL-4 (50 ng/mL) or lipopolysaccharide (LPS; 10 ng/mL). Agaphelin is non-cytotoxic for BEAS-2B cells. Notably, agaphelin markedly reduces CCL2 and IL-8 production induced by IL-4 or LPS, without altering the IL-10 production. The TLR4 expression and STAT1 phosphorylation induced by LPS were inhibited by agaphlin. In addition, agaphelin decreased the phosphorylation of STAT6 induce by IL-4, whose effect was independent of IL-4-binding activity. Taken together, these findings identify agaphelin as a potential anti-inflammatory therapeutic agent for airway inflammations.
Keywords:Bronchial epithelial cells  Agaphelin  IL-4  LPS
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