Trappin-2/elafin modulate innate immune responses of human endometrial epithelial cells to PolyI:C.

PloS one (2012-05-01)
Anna G Drannik, Kakon Nag, Xiao-Dan Yao, Bethany M Henrick, Jean-Michel Sallenave, Kenneth L Rosenthal
RESUMO

Upon viral recognition, innate and adaptive antiviral immune responses are initiated by genital epithelial cells (ECs) to eradicate or contain viral infection. Such responses, however, are often accompanied by inflammation that contributes to acquisition and progression of sexually transmitted infections (STIs). Hence, interventions/factors enhancing antiviral protection while reducing inflammation may prove beneficial in controlling the spread of STIs. Serine antiprotease trappin-2 (Tr) and its cleaved form, elafin (E), are alarm antimicrobials secreted by multiple cells, including genital epithelia. We investigated whether and how each Tr and E (Tr/E) contribute to antiviral defenses against a synthetic mimic of viral dsRNA, polyinosine-polycytidylic acid (polyI:C) and vesicular stomatitis virus. We show that delivery of a replication-deficient adenovector expressing Tr gene (Ad/Tr) to human endometrial epithelial cells, HEC-1A, resulted in secretion of functional Tr, whereas both Tr/E were detected in response to polyI:C. Moreover, Tr/E were found to significantly reduce viral replication by either acting directly on virus or through enhancing polyI:C-driven antiviral protection. The latter was associated with reduced levels of pro-inflammatory factors IL-8, IL-6, TNFα, lowered expression of RIG-I, MDA5 and attenuated NF-κB activation. Interestingly, enhanced polyI:C-driven antiviral protection of HEC-Ad/Tr cells was partially mediated through IRF3 activation, but not associated with higher induction of IFNβ, suggesting multiple antiviral mechanisms of Tr/E and the involvement of alternative factors or pathways. This is the first evidence of both Tr/E altering viral binding/entry, innate recognition and mounting of antiviral and inflammatory responses in genital ECs that could have significant implications for homeostasis of the female genital tract.

MATERIAIS
Número do produto
Marca
Descrição do produto

Sigma-Aldrich
N-Methoxysuccinyl-Ala-Ala-Pro-Val p-nitroanilide, elastase substrate

Redes sociais

LinkedIn icon
Twitter icon
Facebook Icon
Instagram Icon

Merck

Pesquisa. Desenvolvimento. Produção.

Somos um fornecedor global líder para o setor de ciências biológicas, com soluções e serviços para pesquisa, desenvolvimento e produção de biotecnologia, além de produção e desenvolvimento de terapias farmacológicas com medicamentos.

© 2021 Merck KGaA, Darmstadt, Alemanha e/ou suas filiais. Todos os direitos reservados.

A reprodução não autorizada de quaisquer materiais deste site é estritamente proibida.