Limits...
Increased nuclear suppressor of cytokine signaling 1 in asthmatic bronchial epithelium suppresses rhinovirus induction of innate interferons.

Gielen V, Sykes A, Zhu J, Chan B, Macintyre J, Regamey N, Kieninger E, Gupta A, Shoemark A, Bossley C, Davies J, Saglani S, Walker P, Nicholson SE, Dalpke AH, Kon OM, Bush A, Johnston SL, Edwards MR - J. Allergy Clin. Immunol. (2015)

Bottom Line: SOCS1 levels were also correlated with asthma-related clinical outcomes.Suppression of virus-induced interferon levels was dependent on SOCS1 nuclear translocation but independent of proteasomal degradation of transcription factors.Nuclear SOCS1 levels were also increased in BECs from asthmatic patients.

View Article: PubMed Central - PubMed

Affiliation: Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom; MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom; Centre for Respiratory Infection, Imperial College London, London, United Kingdom.

Show MeSH

Related in: MedlinePlus

IL-13 treatment increased lung SOCS1 expression. IFN-γ−/− C57Bl/6 mice were treated with 0.5 μg of IL-13 or PBS (vehicle) through the intranasal (i.n.) route. A, Schematic diagram showing the timing of IL-13/PBS treatment and RV1B/UV-RV1B infection 8 hours later. BAL and lung mRNA was harvested at 8, 24, and 48 hours after infection. B, IL-13 treatment induced SOCS1 mRNA in IFN-γ−/− mice at 4 hours after IL-13 treatment compared with PBS-treated mice. Values are presented as means ± SEMs (n = 4 animals per group). **P < .01, t test.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4541718&req=5

dfig5: IL-13 treatment increased lung SOCS1 expression. IFN-γ−/− C57Bl/6 mice were treated with 0.5 μg of IL-13 or PBS (vehicle) through the intranasal (i.n.) route. A, Schematic diagram showing the timing of IL-13/PBS treatment and RV1B/UV-RV1B infection 8 hours later. BAL and lung mRNA was harvested at 8, 24, and 48 hours after infection. B, IL-13 treatment induced SOCS1 mRNA in IFN-γ−/− mice at 4 hours after IL-13 treatment compared with PBS-treated mice. Values are presented as means ± SEMs (n = 4 animals per group). **P < .01, t test.

Mentions: We next investigated the importance of SOCS1 in regulating rhinovirus-induced interferon in vivo using IFN-γ−/− and SOCS1−/−IFN-γ−/− mice. Mice were pretreated with IL-13 for 8 hours to enhance SOCS1 levels before rhinovirus infection (see Fig E5, A, in this article's Online Repository at www.jacionline.org). IL-13 pretreatment significantly enhanced SOCS1 mRNA expression in the lungs of IFN-γ−/− mice by approximately 3-fold (see Fig E5, B). As expected, there was no SOCS1 expression in SOCS1-deficient mice. On rhinovirus infection, IL-13–pretreated IFN-γ−/− mice in which SOCS1 was induced had significantly deficient IFN-α, trends toward deficient IFN-λ, and significantly deficient RANTES/CCL5 (an interferon-inducible chemokine) in BAL fluid when compared with IL-13–pretreated SOCS1−/−IFN-γ−/− mice, in which SOCS1 could not be induced (Fig 3, C). Consistent with our observation that enhanced SOCS1 expression substantially enhanced rhinovirus induction of the CXCL8 promoter in human BECs in vitro (see Fig E4, A), enhanced SOCS1 expression significantly augmented rhinovirus induction of the mouse CXCL8 homologues keratinocyte-derived chemokine (KC)/CXCL1 and LPS-induced CXC chemokine (LIX)/CXCL5 in vivo (Fig 3, C).


Increased nuclear suppressor of cytokine signaling 1 in asthmatic bronchial epithelium suppresses rhinovirus induction of innate interferons.

Gielen V, Sykes A, Zhu J, Chan B, Macintyre J, Regamey N, Kieninger E, Gupta A, Shoemark A, Bossley C, Davies J, Saglani S, Walker P, Nicholson SE, Dalpke AH, Kon OM, Bush A, Johnston SL, Edwards MR - J. Allergy Clin. Immunol. (2015)

IL-13 treatment increased lung SOCS1 expression. IFN-γ−/− C57Bl/6 mice were treated with 0.5 μg of IL-13 or PBS (vehicle) through the intranasal (i.n.) route. A, Schematic diagram showing the timing of IL-13/PBS treatment and RV1B/UV-RV1B infection 8 hours later. BAL and lung mRNA was harvested at 8, 24, and 48 hours after infection. B, IL-13 treatment induced SOCS1 mRNA in IFN-γ−/− mice at 4 hours after IL-13 treatment compared with PBS-treated mice. Values are presented as means ± SEMs (n = 4 animals per group). **P < .01, t test.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4541718&req=5

dfig5: IL-13 treatment increased lung SOCS1 expression. IFN-γ−/− C57Bl/6 mice were treated with 0.5 μg of IL-13 or PBS (vehicle) through the intranasal (i.n.) route. A, Schematic diagram showing the timing of IL-13/PBS treatment and RV1B/UV-RV1B infection 8 hours later. BAL and lung mRNA was harvested at 8, 24, and 48 hours after infection. B, IL-13 treatment induced SOCS1 mRNA in IFN-γ−/− mice at 4 hours after IL-13 treatment compared with PBS-treated mice. Values are presented as means ± SEMs (n = 4 animals per group). **P < .01, t test.
Mentions: We next investigated the importance of SOCS1 in regulating rhinovirus-induced interferon in vivo using IFN-γ−/− and SOCS1−/−IFN-γ−/− mice. Mice were pretreated with IL-13 for 8 hours to enhance SOCS1 levels before rhinovirus infection (see Fig E5, A, in this article's Online Repository at www.jacionline.org). IL-13 pretreatment significantly enhanced SOCS1 mRNA expression in the lungs of IFN-γ−/− mice by approximately 3-fold (see Fig E5, B). As expected, there was no SOCS1 expression in SOCS1-deficient mice. On rhinovirus infection, IL-13–pretreated IFN-γ−/− mice in which SOCS1 was induced had significantly deficient IFN-α, trends toward deficient IFN-λ, and significantly deficient RANTES/CCL5 (an interferon-inducible chemokine) in BAL fluid when compared with IL-13–pretreated SOCS1−/−IFN-γ−/− mice, in which SOCS1 could not be induced (Fig 3, C). Consistent with our observation that enhanced SOCS1 expression substantially enhanced rhinovirus induction of the CXCL8 promoter in human BECs in vitro (see Fig E4, A), enhanced SOCS1 expression significantly augmented rhinovirus induction of the mouse CXCL8 homologues keratinocyte-derived chemokine (KC)/CXCL1 and LPS-induced CXC chemokine (LIX)/CXCL5 in vivo (Fig 3, C).

Bottom Line: SOCS1 levels were also correlated with asthma-related clinical outcomes.Suppression of virus-induced interferon levels was dependent on SOCS1 nuclear translocation but independent of proteasomal degradation of transcription factors.Nuclear SOCS1 levels were also increased in BECs from asthmatic patients.

View Article: PubMed Central - PubMed

Affiliation: Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom; MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom; Centre for Respiratory Infection, Imperial College London, London, United Kingdom.

Show MeSH
Related in: MedlinePlus