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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, but not SOCS3, mRNA expression was increased in primary BECs from children with severe asthma compared with that seen in control children and was related to impaired interferon induction and increased viral release. A, SOCS1 mRNA levels were increased at baseline in children with STRA compared with NANA subjects. No differences between NANA subjects and children with STRA were observed for SOCS3 mRNA levels. *P < .05. ns, Not significant. B, PolyI:C induced IFN-β, IFN-λ1, and IFNλ2/3 mRNA levels 8 hours after treatment negatively correlated with baseline SOCS1 mRNA levels. C, RV16-induced IFN-β/λ1/λ2/3 mRNA levels 24 hours after infection negatively correlated with baseline SOCS1 mRNA levels. D, RV1B-induced IFN-β/λ1/λ2/3 mRNA levels 24 hours after infection showed trends toward a negative correlation with baseline SOCS1 mRNA levels. E, RV16 and RV1B release 48 hours after infection, as measured by means of titration in HeLa cells, positively correlated with baseline SOCS1 mRNA levels.
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fig4: SOCS1, but not SOCS3, mRNA expression was increased in primary BECs from children with severe asthma compared with that seen in control children and was related to impaired interferon induction and increased viral release. A, SOCS1 mRNA levels were increased at baseline in children with STRA compared with NANA subjects. No differences between NANA subjects and children with STRA were observed for SOCS3 mRNA levels. *P < .05. ns, Not significant. B, PolyI:C induced IFN-β, IFN-λ1, and IFNλ2/3 mRNA levels 8 hours after treatment negatively correlated with baseline SOCS1 mRNA levels. C, RV16-induced IFN-β/λ1/λ2/3 mRNA levels 24 hours after infection negatively correlated with baseline SOCS1 mRNA levels. D, RV1B-induced IFN-β/λ1/λ2/3 mRNA levels 24 hours after infection showed trends toward a negative correlation with baseline SOCS1 mRNA levels. E, RV16 and RV1B release 48 hours after infection, as measured by means of titration in HeLa cells, positively correlated with baseline SOCS1 mRNA levels.

Mentions: BECs from children with STRA with confirmed rhinovirus-induced interferon deficiency14 were used to investigate whether SOCS1 levels are increased in primary BECs from patients with severe asthma. We also sought to establish whether there were relationships between SOCS1 levels, interferon deficiency, and viral replication. SOCS1, but not SOCS3, mRNA expression levels were increased (approximately 8- to 9-fold) in unstimulated and uninfected primary human BECs from children with severe asthma compared with those in BECs from NANA control subjects (Fig 4, A). SOCS1 mRNA levels in the unstimulated and uninfected cells were significantly inversely correlated with IFN-λ1 and IFN-λ2/3 mRNA induction by polyI:C, with a similar but nonsignificant trend for IFN-β (Fig 4, B) and, importantly, with induction of all 3 interferon subtypes by RV16 (Fig 4, C). However, RV1B showed no significant correlation (Fig 4, D). Baseline SOCS1 mRNA levels correlated positively with RV1B release at 48 hours after infection in BECs but did not correlate with RV16 release (Fig 4, E).


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, but not SOCS3, mRNA expression was increased in primary BECs from children with severe asthma compared with that seen in control children and was related to impaired interferon induction and increased viral release. A, SOCS1 mRNA levels were increased at baseline in children with STRA compared with NANA subjects. No differences between NANA subjects and children with STRA were observed for SOCS3 mRNA levels. *P < .05. ns, Not significant. B, PolyI:C induced IFN-β, IFN-λ1, and IFNλ2/3 mRNA levels 8 hours after treatment negatively correlated with baseline SOCS1 mRNA levels. C, RV16-induced IFN-β/λ1/λ2/3 mRNA levels 24 hours after infection negatively correlated with baseline SOCS1 mRNA levels. D, RV1B-induced IFN-β/λ1/λ2/3 mRNA levels 24 hours after infection showed trends toward a negative correlation with baseline SOCS1 mRNA levels. E, RV16 and RV1B release 48 hours after infection, as measured by means of titration in HeLa cells, positively correlated with baseline SOCS1 mRNA levels.
© Copyright Policy - CC BY
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fig4: SOCS1, but not SOCS3, mRNA expression was increased in primary BECs from children with severe asthma compared with that seen in control children and was related to impaired interferon induction and increased viral release. A, SOCS1 mRNA levels were increased at baseline in children with STRA compared with NANA subjects. No differences between NANA subjects and children with STRA were observed for SOCS3 mRNA levels. *P < .05. ns, Not significant. B, PolyI:C induced IFN-β, IFN-λ1, and IFNλ2/3 mRNA levels 8 hours after treatment negatively correlated with baseline SOCS1 mRNA levels. C, RV16-induced IFN-β/λ1/λ2/3 mRNA levels 24 hours after infection negatively correlated with baseline SOCS1 mRNA levels. D, RV1B-induced IFN-β/λ1/λ2/3 mRNA levels 24 hours after infection showed trends toward a negative correlation with baseline SOCS1 mRNA levels. E, RV16 and RV1B release 48 hours after infection, as measured by means of titration in HeLa cells, positively correlated with baseline SOCS1 mRNA levels.
Mentions: BECs from children with STRA with confirmed rhinovirus-induced interferon deficiency14 were used to investigate whether SOCS1 levels are increased in primary BECs from patients with severe asthma. We also sought to establish whether there were relationships between SOCS1 levels, interferon deficiency, and viral replication. SOCS1, but not SOCS3, mRNA expression levels were increased (approximately 8- to 9-fold) in unstimulated and uninfected primary human BECs from children with severe asthma compared with those in BECs from NANA control subjects (Fig 4, A). SOCS1 mRNA levels in the unstimulated and uninfected cells were significantly inversely correlated with IFN-λ1 and IFN-λ2/3 mRNA induction by polyI:C, with a similar but nonsignificant trend for IFN-β (Fig 4, B) and, importantly, with induction of all 3 interferon subtypes by RV16 (Fig 4, C). However, RV1B showed no significant correlation (Fig 4, D). Baseline SOCS1 mRNA levels correlated positively with RV1B release at 48 hours after infection in BECs but did not correlate with RV16 release (Fig 4, E).

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