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Suppressor of cytokine signalling 1 (SOCS1) is a physiological regulator of the asthma response.
Clin Exp Allergy 2009; 39(6):897-907CE

Abstract

BACKGROUND

The molecular determinants of the severity and persistence of allergic asthma remain poorly understood. Suppressor of cytokine signalling 1 (SOCS1) is a negative regulator of IL-4-dependent pathways in vitro and might therefore control T-helper type 2 (Th2) immunity associated traits, such as IgE levels, mucin production, IL-5 and IL-13 induction, and eosinophilic mucosal inflammation, which are implicated in allergic asthma.

OBJECTIVE

To investigate the role of SOCS1 in regulating Th2-associated disease traits in a murine sub-chronic aeroallergen-driven asthma model.

METHODS

Following sensitization and challenge with ovalbumin (OVA), bronchoalveolar lavage and serum were collected from mice lacking the Socs1 gene on an IFN-gamma null background (Socs1(-/-)Ifngamma(-/-)). The composition of infiltrating cells in the lung, serum IgE and IgG1 levels and cytokine levels were analysed.

RESULTS

Serum IgE levels and infiltrating eosinophils were considerably increased in the lungs of OVA-treated Socs1(-/-)Ifngamma(-/-) mice compared with Ifngamma(-/-) and C57BL/6 controls. Expression of the Th2 cytokines, IL-4, IL-5 and IL-13 was increased in CD4+ cells and lung tissue from OVA-treated Socs1(-/-)Ifngamma(-/-) mice. IgE, IL-5 levels and infiltrating eosinophils were also elevated in saline-treated Socs1(-/-)Ifngamma(-/-) mice, suggesting that in the absence of SOCS1, mice are already biased towards a Th2 response. It is at present unclear whether the elevated cytokine levels are sufficient to result in the exacerbated Th2 response to OVA challenge or whether enhanced intra-cellular signalling also contributes. Surprisingly, of the various IL-4/IL-13 responsive genes tested, only Arginase I appeared to be modestly up-regulated in the lungs of OVA-treated Socs1(-/-)Ifngamma(-/-) mice, suggesting that regulation by SOCS1 occurs primarily in haematopoietic cells and not in the airway epithelium.

CONCLUSIONS

Together these results indicate that SOCS1 is an important regulator of the Th2 response.

Authors+Show Affiliations

Department of Medical Biology, The University of Melbourne, Parkville Vic., Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19309352

Citation

Lee, C, et al. "Suppressor of Cytokine Signalling 1 (SOCS1) Is a Physiological Regulator of the Asthma Response." Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, vol. 39, no. 6, 2009, pp. 897-907.
Lee C, Kolesnik TB, Caminschi I, et al. Suppressor of cytokine signalling 1 (SOCS1) is a physiological regulator of the asthma response. Clin Exp Allergy. 2009;39(6):897-907.
Lee, C., Kolesnik, T. B., Caminschi, I., Chakravorty, A., Carter, W., Alexander, W. S., ... Nicholson, S. E. (2009). Suppressor of cytokine signalling 1 (SOCS1) is a physiological regulator of the asthma response. Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, 39(6), pp. 897-907. doi:10.1111/j.1365-2222.2009.03217.x.
Lee C, et al. Suppressor of Cytokine Signalling 1 (SOCS1) Is a Physiological Regulator of the Asthma Response. Clin Exp Allergy. 2009;39(6):897-907. PubMed PMID: 19309352.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Suppressor of cytokine signalling 1 (SOCS1) is a physiological regulator of the asthma response. AU - Lee,C, AU - Kolesnik,T B, AU - Caminschi,I, AU - Chakravorty,A, AU - Carter,W, AU - Alexander,W S, AU - Jones,J, AU - Anderson,G P, AU - Nicholson,S E, Y1 - 2009/03/20/ PY - 2009/3/25/entrez PY - 2009/3/25/pubmed PY - 2009/8/27/medline SP - 897 EP - 907 JF - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology JO - Clin. Exp. Allergy VL - 39 IS - 6 N2 - BACKGROUND: The molecular determinants of the severity and persistence of allergic asthma remain poorly understood. Suppressor of cytokine signalling 1 (SOCS1) is a negative regulator of IL-4-dependent pathways in vitro and might therefore control T-helper type 2 (Th2) immunity associated traits, such as IgE levels, mucin production, IL-5 and IL-13 induction, and eosinophilic mucosal inflammation, which are implicated in allergic asthma. OBJECTIVE: To investigate the role of SOCS1 in regulating Th2-associated disease traits in a murine sub-chronic aeroallergen-driven asthma model. METHODS: Following sensitization and challenge with ovalbumin (OVA), bronchoalveolar lavage and serum were collected from mice lacking the Socs1 gene on an IFN-gamma null background (Socs1(-/-)Ifngamma(-/-)). The composition of infiltrating cells in the lung, serum IgE and IgG1 levels and cytokine levels were analysed. RESULTS: Serum IgE levels and infiltrating eosinophils were considerably increased in the lungs of OVA-treated Socs1(-/-)Ifngamma(-/-) mice compared with Ifngamma(-/-) and C57BL/6 controls. Expression of the Th2 cytokines, IL-4, IL-5 and IL-13 was increased in CD4+ cells and lung tissue from OVA-treated Socs1(-/-)Ifngamma(-/-) mice. IgE, IL-5 levels and infiltrating eosinophils were also elevated in saline-treated Socs1(-/-)Ifngamma(-/-) mice, suggesting that in the absence of SOCS1, mice are already biased towards a Th2 response. It is at present unclear whether the elevated cytokine levels are sufficient to result in the exacerbated Th2 response to OVA challenge or whether enhanced intra-cellular signalling also contributes. Surprisingly, of the various IL-4/IL-13 responsive genes tested, only Arginase I appeared to be modestly up-regulated in the lungs of OVA-treated Socs1(-/-)Ifngamma(-/-) mice, suggesting that regulation by SOCS1 occurs primarily in haematopoietic cells and not in the airway epithelium. CONCLUSIONS: Together these results indicate that SOCS1 is an important regulator of the Th2 response. SN - 1365-2222 UR - https://www.unboundmedicine.com/medline/citation/19309352/Suppressor_of_cytokine_signalling_1__SOCS1__is_a_physiological_regulator_of_the_asthma_response_ L2 - https://doi.org/10.1111/j.1365-2222.2009.03217.x DB - PRIME DP - Unbound Medicine ER -