Modulation of inflammation and pathology during dengue virus infection by p38 MAPK inhibitor SB203580

Yilong Fu, Andy Yip, Peck Gee Seah, Francesca Blasco, Pei-Yong Shi, Maxime Hervé

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Dengue virus (DENV) infection could lead to dengue fever (DF), dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). The disease outcome is controlled by both viral and host factors. Inflammation mediators from DENV-infected cells could contribute to increased vascular permeability, leading to severe DHF/DSS. Therefore, suppression of inflammation could be a potential therapeutic approach for treatment of dengue patients. In this context, p38 MAPK (mitogen-activated protein kinase) is a key enzyme that modulates the initiation of stress and inflammatory responses. Here we show that SB203580, a p38 MAPK inhibitor, suppressed the over production of DENV-induced pro-inflammatory mediators such as TNF-α, IL-8, and RANTES from human PBMCs, monocytic THP-1, and granulocyte KU812 cell lines. Oral administration of SB203580 in DENV-infected AG129 mice prevented hematocrit rise and lymphopenia, limited the development of inflammation and pathology (including intestine leakage), and significantly improved survival. These results, for the first time, have provided experimental evidence to imply that a short term inhibition of p38 MAPK may be beneficial to reduce disease symptoms in dengue patients.

Original languageEnglish (US)
Pages (from-to)151-157
Number of pages7
JournalAntiviral Research
Volume110
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Severe Dengue
Dengue Virus
p38 Mitogen-Activated Protein Kinases
Virus Diseases
Protein Kinase Inhibitors
Pathology
Inflammation
Dengue
Inflammation Mediators
Chemokine CCL5
Lymphopenia
Capillary Permeability
Interleukin-8
Hematocrit
Granulocytes
Intestines
Oral Administration
SB 203580
Cell Line
Survival

Keywords

  • Antiviral drug discovery
  • Dengue therapeutics
  • Dengue virus
  • p38 MAPK

ASJC Scopus subject areas

  • Virology
  • Pharmacology
  • Medicine(all)

Cite this

Modulation of inflammation and pathology during dengue virus infection by p38 MAPK inhibitor SB203580. / Fu, Yilong; Yip, Andy; Seah, Peck Gee; Blasco, Francesca; Shi, Pei-Yong; Hervé, Maxime.

In: Antiviral Research, Vol. 110, 2014, p. 151-157.

Research output: Contribution to journalArticle

Fu, Yilong ; Yip, Andy ; Seah, Peck Gee ; Blasco, Francesca ; Shi, Pei-Yong ; Hervé, Maxime. / Modulation of inflammation and pathology during dengue virus infection by p38 MAPK inhibitor SB203580. In: Antiviral Research. 2014 ; Vol. 110. pp. 151-157.
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