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| [PMID]: | 28494003 |
| [Au] Autor: | Huipao N; Borwornpinyo S; Wiboon-Ut S; Campbell CR; Lee IH; Hiranyachattada S; Sukasem C; Thitithanyanont A; Pholpramool C; Cook DI; Dinudom A |
| [Ad] Endereço: | Department of Physiology, Faculty of Science, Prince of Songkla University, Songkhla, Thailand. |
| [Ti] Título: | P2Y6 receptors are involved in mediating the effect of inactivated avian influenza virus H5N1 on IL-6 & CXCL8 mRNA expression in respiratory epithelium. |
| [So] Source: | PLoS One;12(5):e0176974, 2017. | | [Is] ISSN: | 1932-6203 |
| [Cp] País de publicação: | United States |
| [La] Idioma: | eng |
| [Ab] Resumo: | One of the key pathophysiologies of H5N1 infection is excessive proinflammatory cytokine response (cytokine storm) characterized by increases in IFN-ß, TNF-α, IL-6, CXCL10, CCL4, CCL2 and CCL5 in the respiratory tract. H5N1-induced cytokine release can occur via an infection-independent mechanism, however, detail of the cellular signaling involved is poorly understood. To elucidate this mechanism, the effect of inactivated (ß-propiolactone-treated) H5N1 on the cytokine and chemokine mRNA expression in 16HBE14o- human respiratory epithelial cells was investigated. We found that the inactivated-H5N1 increased mRNA for IL-6 and CXCL8 but not TNF-α, CCL5 or CXCL10. This effect of the inactivated-H5N1 was inhibited by sialic acid receptor inhibitor (α-2,3 sialidase), adenosine diphosphatase (apyrase), P2Y receptor (P2YR) inhibitor (suramin), P2Y6R antagonist (MRS2578), phospholipase C inhibitor (U73122), protein kinase C inhibitors (BIM and Gö6976) and cell-permeant Ca2+ chelator (BAPTA-AM). Inhibitors of MAPK signaling, including of ERK1/2 (PD98059), p38 MAPK (SB203580) and JNK (SP600125) significantly suppressed the inactivated-H5N1-induced mRNA expression of CXCL8. On the other hand, the inactivated-H5N1-induced mRNA expression of IL-6 was inhibited by SB203580, but not PD98059 or SP600125, whereas SN-50, an inhibitor of NF-κB, inhibited the effect of virus on mRNA expression of both of IL-6 and CXCL8. Taken together, our data suggest that, without infection, inactivated-H5N1 induces mRNA expression of IL-6 and CXCL8 by a mechanism, or mechanisms, requiring interaction between viral hemagglutinin and α-2,3 sialic acid receptors at the cell membrane of host cells, and involves activation of P2Y6 purinergic receptors. |
| [Mh] Termos MeSH primário: |
Regulação da Expressão Gênica
Vírus da Influenza A Subtipo H5N1/fisiologia
Influenza Humana/genética
Interleucina-6/genética
Interleucina-8/genética
Receptores Purinérgicos P2/metabolismo
Mucosa Respiratória/virologia
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| [Mh] Termos MeSH secundário: |
Animais
Linhagem Celular
Galinhas
Seres Humanos
Influenza Humana/metabolismo
Influenza Humana/virologia
RNA Mensageiro/genética
Mucosa Respiratória/metabolismo
Transdução de Sinais
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| [Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (IL8 protein, human); 0 (Interleukin-6); 0 (Interleukin-8); 0 (RNA, Messenger); 0 (Receptors, Purinergic P2); 0 (purinoceptor P2Y6) |
| [Em] Mês de entrada: | 1709 |
| [Cu] Atualização por classe: | 170919 |
[Lr] Data última revisão:
| 170919 |
| [Sb] Subgrupo de revista: | IM |
| [Da] Data de entrada para processamento: | 170512 |
| [St] Status: | MEDLINE |
| [do] DOI: | 10.1371/journal.pone.0176974 |
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