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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.

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SOCS1 suppressed rhinovirus-induced interferon induction but not rhinovirus-induced proinflammatory cytokine induction. A, SOCS1-transfected cells showed completely suppressed RV1B-induced IFN-β and IFN-λ1 promoter activation versus pORF empty vector control at 24 hours. ***P < .001. B, RV1B-induced IFN-β mRNA expression was increased in ex vivo–cultured BAL macrophages from SOCS1−/−IFN-γ−/− mice compared with IFN-γ−/− mice. No differences were observed between these 2 groups for RV1B-induced TNF-α mRNA. *P < .05. C, RV1B-induced IFN-α expression (8 hours after infection) was significantly increased in RV1B-infected SOCS1−/−IFN-γ−/− mice compared with IFN-γ−/− mice. BAL IFN-λ (24 hours) levels showed a nonsignificant trend for increase in RV1B-infected SOCS1−/−IFN-γ−/− mice, whereas CCL5 levels (24 hours) were also significantly increased in RV1B-infected SOCS1−/−IFN-γ−/− mice compared with IFN-γ−/− mice. CXCL1/KC and LIX/CXCL5 (both 48 hours) were both decreased in BAL fluid from RV1B-infected SOCS1−/−IFN-γ−/− mice compared with IFN-γ−/− mice. A mixture of SOCS1−/−IFN-γ−/− and IFN-γ−/− mice was used for the UV-RV1B and UV-RV1B plus IL-13 groups. *P < .05 and ***P < .001. ns, Not significant.
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fig3: SOCS1 suppressed rhinovirus-induced interferon induction but not rhinovirus-induced proinflammatory cytokine induction. A, SOCS1-transfected cells showed completely suppressed RV1B-induced IFN-β and IFN-λ1 promoter activation versus pORF empty vector control at 24 hours. ***P < .001. B, RV1B-induced IFN-β mRNA expression was increased in ex vivo–cultured BAL macrophages from SOCS1−/−IFN-γ−/− mice compared with IFN-γ−/− mice. No differences were observed between these 2 groups for RV1B-induced TNF-α mRNA. *P < .05. C, RV1B-induced IFN-α expression (8 hours after infection) was significantly increased in RV1B-infected SOCS1−/−IFN-γ−/− mice compared with IFN-γ−/− mice. BAL IFN-λ (24 hours) levels showed a nonsignificant trend for increase in RV1B-infected SOCS1−/−IFN-γ−/− mice, whereas CCL5 levels (24 hours) were also significantly increased in RV1B-infected SOCS1−/−IFN-γ−/− mice compared with IFN-γ−/− mice. CXCL1/KC and LIX/CXCL5 (both 48 hours) were both decreased in BAL fluid from RV1B-infected SOCS1−/−IFN-γ−/− mice compared with IFN-γ−/− mice. A mixture of SOCS1−/−IFN-γ−/− and IFN-γ−/− mice was used for the UV-RV1B and UV-RV1B plus IL-13 groups. *P < .05 and ***P < .001. ns, Not significant.

Mentions: Overexpression of SOCS1 also completely suppressed rhinovirus-induced IFN-β and IFN-λ1 promoter activation in primary human BECs (Fig 3, A). In contrast, overexpression of SOCS1 in BEAS-2B cells significantly increased rhinovirus-, IL-1β–, and TNF-α–induced CXCL8 promoter activation (around 20- to 25-fold; see Fig E4 in this article's Online Repository at www.jacionline.org).


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)

SOCS1 suppressed rhinovirus-induced interferon induction but not rhinovirus-induced proinflammatory cytokine induction. A, SOCS1-transfected cells showed completely suppressed RV1B-induced IFN-β and IFN-λ1 promoter activation versus pORF empty vector control at 24 hours. ***P < .001. B, RV1B-induced IFN-β mRNA expression was increased in ex vivo–cultured BAL macrophages from SOCS1−/−IFN-γ−/− mice compared with IFN-γ−/− mice. No differences were observed between these 2 groups for RV1B-induced TNF-α mRNA. *P < .05. C, RV1B-induced IFN-α expression (8 hours after infection) was significantly increased in RV1B-infected SOCS1−/−IFN-γ−/− mice compared with IFN-γ−/− mice. BAL IFN-λ (24 hours) levels showed a nonsignificant trend for increase in RV1B-infected SOCS1−/−IFN-γ−/− mice, whereas CCL5 levels (24 hours) were also significantly increased in RV1B-infected SOCS1−/−IFN-γ−/− mice compared with IFN-γ−/− mice. CXCL1/KC and LIX/CXCL5 (both 48 hours) were both decreased in BAL fluid from RV1B-infected SOCS1−/−IFN-γ−/− mice compared with IFN-γ−/− mice. A mixture of SOCS1−/−IFN-γ−/− and IFN-γ−/− mice was used for the UV-RV1B and UV-RV1B plus IL-13 groups. *P < .05 and ***P < .001. ns, Not significant.
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fig3: SOCS1 suppressed rhinovirus-induced interferon induction but not rhinovirus-induced proinflammatory cytokine induction. A, SOCS1-transfected cells showed completely suppressed RV1B-induced IFN-β and IFN-λ1 promoter activation versus pORF empty vector control at 24 hours. ***P < .001. B, RV1B-induced IFN-β mRNA expression was increased in ex vivo–cultured BAL macrophages from SOCS1−/−IFN-γ−/− mice compared with IFN-γ−/− mice. No differences were observed between these 2 groups for RV1B-induced TNF-α mRNA. *P < .05. C, RV1B-induced IFN-α expression (8 hours after infection) was significantly increased in RV1B-infected SOCS1−/−IFN-γ−/− mice compared with IFN-γ−/− mice. BAL IFN-λ (24 hours) levels showed a nonsignificant trend for increase in RV1B-infected SOCS1−/−IFN-γ−/− mice, whereas CCL5 levels (24 hours) were also significantly increased in RV1B-infected SOCS1−/−IFN-γ−/− mice compared with IFN-γ−/− mice. CXCL1/KC and LIX/CXCL5 (both 48 hours) were both decreased in BAL fluid from RV1B-infected SOCS1−/−IFN-γ−/− mice compared with IFN-γ−/− mice. A mixture of SOCS1−/−IFN-γ−/− and IFN-γ−/− mice was used for the UV-RV1B and UV-RV1B plus IL-13 groups. *P < .05 and ***P < .001. ns, Not significant.
Mentions: Overexpression of SOCS1 also completely suppressed rhinovirus-induced IFN-β and IFN-λ1 promoter activation in primary human BECs (Fig 3, A). In contrast, overexpression of SOCS1 in BEAS-2B cells significantly increased rhinovirus-, IL-1β–, and TNF-α–induced CXCL8 promoter activation (around 20- to 25-fold; see Fig E4 in this article's Online Repository at www.jacionline.org).

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