p38 MAP kinase is required for STAT1 serine phosphorylation and transcriptional activation induced by interferons

Goh, Kunli; Haque, S. Jaharul; Williams, Bryan R.G.

doi:10.1093/emboj/18.20.5601

Cited by 341 publications

(295 citation statements)

References 40 publications

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“…Consistent with previous results [46,47], Stat1a was strongly phosphorylated on Ser727 by IFN-a (Fig. 7B, lane 2, %phosphoserine/Stat1a: 69.0 AE 1.9).…”

Section: Influenza a Virus Inhibits Ifn-a-induced Tyrosine And Serinesupporting

confidence: 92%

Influenza A virus abrogates IFN‐γ response in respiratory epithelial cells by disruption of the Jak/Stat pathway

et al. 2008

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The innate immunity to viral infections induces a potent antiviral response mediated by interferons (IFN). Although IFN-c is detected during the acute stages of illness in the upper respiratory tract secretions and in the serum of influenza A virus-infected individuals, control of influenza A virus is not dependent upon IFN-c as evidenced by studies using anti-IFN-c Ab and IFN-c -/-mice. Thus, we hypothesized that IFN-c is not critical in host survival because influenza A virus has mechanisms to evade the antiviral activity of IFN-c. To test this, A549 cells, an epithelial cell line derived from lung adenocarcinoma, were infected with influenza virus strain A/Aichi/2/68 (H3N2) (Aichi) and/or stimulated with IFN-c to detect IFN-c-stimulated MHC class II expression. Influenza A virus infection inhibited IFN-c-induced up-regulation of HLA-DRa mRNA and the IFN-c induction of class II transactivator (CIITA), an obligate mediator of MHC class II expression. Nuclear translocation of Stat1a upon IFN-c stimulation was significantly inhibited in influenza A virus-infected cells and this was associated with a decrease in Tyr701 and Ser727 phosphorylation of Stat1a. Thus, influenza A virus subverts antiviral host defense mediated by IFN-c through effects on the intracellular signaling pathways. IntroductionInfluenza A viruses are negative-strand RNA viruses that have a segmented genome with a coding capacity for 11 polypeptides. The virus genome is composed of eight different RNA segments, which are tightly associated with the viral nucleoprotein and polymerases in ribonucleoprotein complexes [1]. Influenza A viruses, causing acute infections, continuously escape from recognition by virus neutralizing Ab as a result of accumulation of mutations in their surface glycoproteins hemagglutinin and neuraminidase (antigenic drift) or by introduction of new subtypes of these glycoproteins (antigenic shift) [2,3]. Recent outbreaks of highly pathogenic avian influenza A virus infections in poultry and in humans have raised concerns that a new influenza pandemic will occur in the near future [4]. Thus, prediction of the severity of continuously emerging human influenza virus strains remains a high public health priority, but it is limited by our incomplete understanding of the molecular determinants of pathogenicity in this disease. Although factors dictating the severity of virus disease are complex, interaction between inherent viral properties and host cellular response ultimately determines disease outcome. The first site of viral contact with the host and main target of infection and inflammation is the airway mucosal epithelium. Epithelial cells at the airway mucosal surface have a variety of inflammatory and immune defense mechanisms to deal with virus, including Eur. J. Immunol. 2008. 38: 1559-1573 Immunity to infection expression of cytokines with chemoattractant and proinflammatory functions [5], intercellular adhesion molecule-1 (ICAM-1) [6], IFN regulatory factor 1 (IRF-1) [7], nitric oxide synthase 2 (NOS2) [8], and MHC ...

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“…Consistent with previous results [46,47], Stat1a was strongly phosphorylated on Ser727 by IFN-a (Fig. 7B, lane 2, %phosphoserine/Stat1a: 69.0 AE 1.9).…”

Section: Influenza a Virus Inhibits Ifn-a-induced Tyrosine And Serinesupporting

confidence: 92%

Influenza A virus abrogates IFN‐γ response in respiratory epithelial cells by disruption of the Jak/Stat pathway

et al. 2008

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“…Phosphorylations of STAT1 and STAT3 at the Tyr701 or Tyr705 residues, respectively, induce their dimerization, nuclear translocation, and DNA binding [6,17]. In our study, IL-27 alone induced tyrosine phosphorylation of STAT1 (Fig.…”

Section: Expression Of Il-12 Il-23 and Il-27 Receptor Subunits In Hsupporting

confidence: 58%

“…IL-12, IL-23, and IL-27 activate JAK2 and TYK2, and IL-27 simultaneously activates JAK1 JAK catalyze the tyrosine phosphorylation of STAT [2,17] and are constitutively associated with cytokine receptors. Ligand binding to the receptors induces dimerization or oligomerization of receptor subunits and allows juxtaposition, activation, and autoor cross-phosphorylation of the associated JAK [2,17,18].…”

Section: Expression Of Il-12 Il-23 and Il-27 Receptor Subunits In Hmentioning

confidence: 99%

“…Ligand binding to the receptors induces dimerization or oligomerization of receptor subunits and allows juxtaposition, activation, and autoor cross-phosphorylation of the associated JAK [2,17,18]. We thus examined whether IL-12, IL-23, and IL-27 can induce tyrosine phosphorylation of JAK, namely, JAK1, JAK2, and TYK2, in keratinocytes.…”

Section: Expression Of Il-12 Il-23 and Il-27 Receptor Subunits In Hmentioning

confidence: 99%

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IL‐12, IL‐23, and IL‐27 enhance human β‐defensin‐2 production in human keratinocytes

Kanda¹,

Watanabe²

2008

Eur J Immunol

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IL-12, IL-23, and IL-27, which are produced by APC, modulate innate and adaptive immunities. Human b-defensin-2 (hBD-2) produced by epidermal keratinocytes promotes cutaneous antimicrobial defense and inflammation. We examined the in vitro effects of IL-12, IL-23, and IL-27 on hBD-2 production in human keratinocytes. IL-12, IL-23, and IL-27 enhanced IL-1b-induced hBD-2 secretion and mRNA expression in keratinocytes. The stimulatory effects of IL-12, IL-23, and IL-27 were suppressed by antisense oligonucleotides against NF-jB p50 and p65. In addition, the effects of IL-12 and IL-27 were suppressed by antisense STAT3 and STAT1, respectively. All the three IL enhanced the basal and IL-1b-induced transcriptional activities of NF-jB, while IL-12 and IL-27 enhanced STAT3 and STAT1 activities, respectively. Further, IL-12, IL-23, and IL-27 promoted basal and IL-1b-induced phosphorylation of IjBa. IL-12 and IL-23 tyrosine phosphorylated STAT3 and STAT1, respectively; IL-12, IL-23, and IL-27 tyrosine phosphorylated JAK2 and tyrosine kinase-2; and IL-27 tyrosine phosphorylated JAK1. These results suggest that IL-12, IL-23, and IL-27 may enhance IL-1b-induced hBD-2 production in keratinocytes by activating NF-jB. STAT3 and STAT1 are involved in the effects of IL-12 and IL-27, respectively. Thus, IL-12, IL-23, and IL-27 may promote cutaneous antimicrobial defense and inflammation via hBD-2.

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“…Fish IFN exerts its multiple functions, at least antiviral action, through a JAK -STAT pathway. In mammals, apart from the JAK -STAT signal transduction pathway, additional pathways of signal transduction, possibly involving the RNA-dependent protein kinase (PKR) [58], mitogen-activated protein kinase [59,60], and phosphatidylinositol 3-kinase [61], may also be operative under some circumstances. We have also cloned PKR gene and TLR3 gene that are activated by ds RNA [62], and demonstrated that they are also expressed in response to ds RNA virus GCHV [26].…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization and IFN signal pathway analysis of Carassius auratus CaSTAT1 identified from the cultured cells in response to virus infection

Zhang

Gui

2004

Developmental & Comparative Immunology

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p38 MAP kinase is required for STAT1 serine phosphorylation and transcriptional activation induced by interferons

Cited by 341 publications

References 40 publications

Influenza A virus abrogates IFN‐γ response in respiratory epithelial cells by disruption of the Jak/Stat pathway

Influenza A virus abrogates IFN‐γ response in respiratory epithelial cells by disruption of the Jak/Stat pathway

IL‐12, IL‐23, and IL‐27 enhance human β‐defensin‐2 production in human keratinocytes

Molecular characterization and IFN signal pathway analysis of Carassius auratus CaSTAT1 identified from the cultured cells in response to virus infection

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