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

Densitometry of SOCS1 Western blots in Fig 1, effects of SOCS1 mRNA induction by rhinovirus after UV inactivation and filtration, and dose-dependent induction of SOCS1 mRNA by rhinovirus. A-C, Primary human BECs were treated with IL-4 or IL-13 (Fig E1, A) or TNF-α or IL-1β (Fig E1, B) or were infected with RV1B, RV16, or polyI:C (1 μg/mL; Fig E1, C), and total protein was harvested over time and plotted versus α-tubulin as a control protein (n = 1 experiment for all induced SOCS1 protein). D and E, BECs were infected with RV16 (Fig E1, D), UV-inactivated RV16, or filtered RV16, or RV1B (Fig E1, E). F-RVIB, Filtered RV1B; UV-RV1B, UV-inactivated RV1B. UV-inactivated and rhinovirus-filtered (virus-free) preparations both showed a reduction in SOCS1 mRNA expression. F and G, BECs infected with RV16 (Fig E1, F) or RV1B (Fig E1, G) showed dose-dependent inductions of SOCS1 mRNA. *P < .05, **P < .01, and ***P < .001, as indicated or versus rhinovirus treatment, by means of 1-way ANOVA. ns, Not significant. There were 3 to 4 experiments from BECs derived from 3 to 4 healthy control donors.
© Copyright Policy - CC BY
Related In: Results  -  Collection

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

dfig1: Densitometry of SOCS1 Western blots in Fig 1, effects of SOCS1 mRNA induction by rhinovirus after UV inactivation and filtration, and dose-dependent induction of SOCS1 mRNA by rhinovirus. A-C, Primary human BECs were treated with IL-4 or IL-13 (Fig E1, A) or TNF-α or IL-1β (Fig E1, B) or were infected with RV1B, RV16, or polyI:C (1 μg/mL; Fig E1, C), and total protein was harvested over time and plotted versus α-tubulin as a control protein (n = 1 experiment for all induced SOCS1 protein). D and E, BECs were infected with RV16 (Fig E1, D), UV-inactivated RV16, or filtered RV16, or RV1B (Fig E1, E). F-RVIB, Filtered RV1B; UV-RV1B, UV-inactivated RV1B. UV-inactivated and rhinovirus-filtered (virus-free) preparations both showed a reduction in SOCS1 mRNA expression. F and G, BECs infected with RV16 (Fig E1, F) or RV1B (Fig E1, G) showed dose-dependent inductions of SOCS1 mRNA. *P < .05, **P < .01, and ***P < .001, as indicated or versus rhinovirus treatment, by means of 1-way ANOVA. ns, Not significant. There were 3 to 4 experiments from BECs derived from 3 to 4 healthy control donors.

Mentions: SOCS3 mRNA expression is increased in T cells in asthmatic patients,20 but upregulation of SOCS1 by IL-13 in airway smooth muscle cells from asthmatic patients is impaired.22 Thus whether SOCS proteins are upregulated in asthmatic patients is uncertain, and whether SOCS proteins are upregulated in cells that are infected by respiratory tract viruses is unknown. Therefore we first investigated the effects of the TH2 cytokines IL-4 and IL-13 on SOCS1 through SOCS6 and CISH mRNA and protein expression in BECs because these cytokines are strongly implicated in asthma pathogenesis.29,30 IL-4 and IL-13 both induced SOCS1 mRNA and protein expression (Fig 1, A). Densitometric analysis for the Western blots in Fig 1 are shown in Fig E1 in this article's Online Repository at www.jacionline.org. No other SOCS proteins/mRNAs were induced by IL-4 or IL-13, with the exception of CISH, which was significantly induced by both.


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)

Densitometry of SOCS1 Western blots in Fig 1, effects of SOCS1 mRNA induction by rhinovirus after UV inactivation and filtration, and dose-dependent induction of SOCS1 mRNA by rhinovirus. A-C, Primary human BECs were treated with IL-4 or IL-13 (Fig E1, A) or TNF-α or IL-1β (Fig E1, B) or were infected with RV1B, RV16, or polyI:C (1 μg/mL; Fig E1, C), and total protein was harvested over time and plotted versus α-tubulin as a control protein (n = 1 experiment for all induced SOCS1 protein). D and E, BECs were infected with RV16 (Fig E1, D), UV-inactivated RV16, or filtered RV16, or RV1B (Fig E1, E). F-RVIB, Filtered RV1B; UV-RV1B, UV-inactivated RV1B. UV-inactivated and rhinovirus-filtered (virus-free) preparations both showed a reduction in SOCS1 mRNA expression. F and G, BECs infected with RV16 (Fig E1, F) or RV1B (Fig E1, G) showed dose-dependent inductions of SOCS1 mRNA. *P < .05, **P < .01, and ***P < .001, as indicated or versus rhinovirus treatment, by means of 1-way ANOVA. ns, Not significant. There were 3 to 4 experiments from BECs derived from 3 to 4 healthy control donors.
© Copyright Policy - CC BY
Related In: Results  -  Collection

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

dfig1: Densitometry of SOCS1 Western blots in Fig 1, effects of SOCS1 mRNA induction by rhinovirus after UV inactivation and filtration, and dose-dependent induction of SOCS1 mRNA by rhinovirus. A-C, Primary human BECs were treated with IL-4 or IL-13 (Fig E1, A) or TNF-α or IL-1β (Fig E1, B) or were infected with RV1B, RV16, or polyI:C (1 μg/mL; Fig E1, C), and total protein was harvested over time and plotted versus α-tubulin as a control protein (n = 1 experiment for all induced SOCS1 protein). D and E, BECs were infected with RV16 (Fig E1, D), UV-inactivated RV16, or filtered RV16, or RV1B (Fig E1, E). F-RVIB, Filtered RV1B; UV-RV1B, UV-inactivated RV1B. UV-inactivated and rhinovirus-filtered (virus-free) preparations both showed a reduction in SOCS1 mRNA expression. F and G, BECs infected with RV16 (Fig E1, F) or RV1B (Fig E1, G) showed dose-dependent inductions of SOCS1 mRNA. *P < .05, **P < .01, and ***P < .001, as indicated or versus rhinovirus treatment, by means of 1-way ANOVA. ns, Not significant. There were 3 to 4 experiments from BECs derived from 3 to 4 healthy control donors.
Mentions: SOCS3 mRNA expression is increased in T cells in asthmatic patients,20 but upregulation of SOCS1 by IL-13 in airway smooth muscle cells from asthmatic patients is impaired.22 Thus whether SOCS proteins are upregulated in asthmatic patients is uncertain, and whether SOCS proteins are upregulated in cells that are infected by respiratory tract viruses is unknown. Therefore we first investigated the effects of the TH2 cytokines IL-4 and IL-13 on SOCS1 through SOCS6 and CISH mRNA and protein expression in BECs because these cytokines are strongly implicated in asthma pathogenesis.29,30 IL-4 and IL-13 both induced SOCS1 mRNA and protein expression (Fig 1, A). Densitometric analysis for the Western blots in Fig 1 are shown in Fig E1 in this article's Online Repository at www.jacionline.org. No other SOCS proteins/mRNAs were induced by IL-4 or IL-13, with the exception of CISH, which was significantly induced by both.

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