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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 protein levels were increased in bronchial biopsy specimens from adults with mild-to-moderate AA compared with those seen in NANA adults and correlated with asthma-related clinical outcomes. A, Representative pictures showing epithelial staining of SOCS1 (left panels) and SOCS3 (right panels). Bar = 10-μm scale (×40 objective was used in all pictures). Patients with AA showed significantly more SOCS1, but not SOCS3, staining compared with that seen in NANA subjects. *P < .05, bar represents median. ns, Not significant. B, SOCS1 bronchial biopsy scores positively correlated with the number of positive skin pick test responses (SPTs) and negatively correlated with the dose of histamine causing a 20% reduction in lung function (PC20).
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fig2: SOCS1 protein levels were increased in bronchial biopsy specimens from adults with mild-to-moderate AA compared with those seen in NANA adults and correlated with asthma-related clinical outcomes. A, Representative pictures showing epithelial staining of SOCS1 (left panels) and SOCS3 (right panels). Bar = 10-μm scale (×40 objective was used in all pictures). Patients with AA showed significantly more SOCS1, but not SOCS3, staining compared with that seen in NANA subjects. *P < .05, bar represents median. ns, Not significant. B, SOCS1 bronchial biopsy scores positively correlated with the number of positive skin pick test responses (SPTs) and negatively correlated with the dose of histamine causing a 20% reduction in lung function (PC20).

Mentions: We next investigated the abundance of SOCS1 and SOCS3 proteins in biopsy specimens of adults with uninfected mild-to-moderate atopic asthma (AA) compared with nonatopic nonasthmatic (NANA) adult control donors. SOCS1, but not SOCS3, staining intensity was significantly increased in the bronchial epithelium of patients with AA compared with that seen in healthy NANA subjects (Fig 2, A). There was a positive correlation between SOCS1 staining scores and numbers of positive skin prick test responses, with a similar nonsignificant trend for IgE levels (data not shown) and a negative correlation with the provocative concentration of histamine causing a 20% reduction in lung function (PC20 histamine), indicating greater intensity of SOCS1 staining was related to greater severity of atopy and airway hyperresponsiveness (Fig 2, B). In contrast, SOCS3 biopsy staining scores did not significantly correlate with any clinical outcome. SOC1 protein expression did not correlate with numbers of exacerbations (data not shown).


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 protein levels were increased in bronchial biopsy specimens from adults with mild-to-moderate AA compared with those seen in NANA adults and correlated with asthma-related clinical outcomes. A, Representative pictures showing epithelial staining of SOCS1 (left panels) and SOCS3 (right panels). Bar = 10-μm scale (×40 objective was used in all pictures). Patients with AA showed significantly more SOCS1, but not SOCS3, staining compared with that seen in NANA subjects. *P < .05, bar represents median. ns, Not significant. B, SOCS1 bronchial biopsy scores positively correlated with the number of positive skin pick test responses (SPTs) and negatively correlated with the dose of histamine causing a 20% reduction in lung function (PC20).
© Copyright Policy - CC BY
Related In: Results  -  Collection

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

fig2: SOCS1 protein levels were increased in bronchial biopsy specimens from adults with mild-to-moderate AA compared with those seen in NANA adults and correlated with asthma-related clinical outcomes. A, Representative pictures showing epithelial staining of SOCS1 (left panels) and SOCS3 (right panels). Bar = 10-μm scale (×40 objective was used in all pictures). Patients with AA showed significantly more SOCS1, but not SOCS3, staining compared with that seen in NANA subjects. *P < .05, bar represents median. ns, Not significant. B, SOCS1 bronchial biopsy scores positively correlated with the number of positive skin pick test responses (SPTs) and negatively correlated with the dose of histamine causing a 20% reduction in lung function (PC20).
Mentions: We next investigated the abundance of SOCS1 and SOCS3 proteins in biopsy specimens of adults with uninfected mild-to-moderate atopic asthma (AA) compared with nonatopic nonasthmatic (NANA) adult control donors. SOCS1, but not SOCS3, staining intensity was significantly increased in the bronchial epithelium of patients with AA compared with that seen in healthy NANA subjects (Fig 2, A). There was a positive correlation between SOCS1 staining scores and numbers of positive skin prick test responses, with a similar nonsignificant trend for IgE levels (data not shown) and a negative correlation with the provocative concentration of histamine causing a 20% reduction in lung function (PC20 histamine), indicating greater intensity of SOCS1 staining was related to greater severity of atopy and airway hyperresponsiveness (Fig 2, B). In contrast, SOCS3 biopsy staining scores did not significantly correlate with any clinical outcome. SOC1 protein expression did not correlate with numbers of exacerbations (data not shown).

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