IL‐6 promotes acute and chronic inflammatory disease in the absence of SOCS3
| العنوان: | IL‐6 promotes acute and chronic inflammatory disease in the absence of SOCS3 |
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| المؤلفون: | Jesse G. Toe, Joanne A. O’Donnell, Donald Metcalf, Hiu Kiu, Warren S. Alexander, Simon P. Preston, Kate McArthur, Andrew W. Roberts, Marc Pellegrini, Louise H. Cengia, Nicos A. Nicola, Ben A. Croker |
| المصدر: | Immunology and cell biology |
| بيانات النشر: | Wiley, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Male, medicine.medical_treatment, Interleukin-1beta, Arthritis, Apoptosis, Suppressor of Cytokine Signaling Proteins, CD8-Positive T-Lymphocytes, Mice, 0302 clinical medicine, Lymphocytic choriomeningitis virus, Immunology and Allergy, SOCS3, Lymphocytes, Mice, Knockout, 0303 health sciences, biology, digestive, oral, and skin physiology, Flow Cytometry, 3. Good health, Haematopoiesis, Cytokine, medicine.anatomical_structure, IL-1β, 030220 oncology & carcinogenesis, Acute Disease, Cytokines, Female, medicine.symptom, Signal Transduction, Immunology, Inflammation, Spleen, Lymphocytic Choriomeningitis, Article, 03 medical and health sciences, In vivo, medicine, Animals, Interleukin 6, 030304 developmental biology, IL-6, Interleukin-6, Cell Biology, medicine.disease, Survival Analysis, Suppressor of Cytokine Signaling-3, Mice, Inbred C57BL, Suppressor of Cytokine Signaling 3 Protein, Chronic Disease, biology.protein |
| الوصف: | The lack of expression of the suppressor of cytokine signalling-3 (SOCS3) or inactivation of the negative regulatory capacity of SOCS3 has been well documented in rheumatoid arthritis, viral hepatitis and cancer. The specific qualitative and quantitative consequences of SOCS3 deficiency on interleukin-6 (IL-6)-mediated pro- and anti-inflammatory responses remain controversial in vitro and unknown in vivo. Mice with a conditional deletion of SOCS3 in hematopoietic cells develop lethal inflammatory disease during adult life and develop gross histopathological changes during experimental arthritis, typified by elevated IL-6 levels. To clarify the nature of the IL-6 responses in vivo, we generated mice deficient in SOCS3 (SOCS3(-/Δvav)) or both SOCS3 and IL-6 (IL-6(-/-)/SOCS3(-/Δvav)), and examined responses in models of acute and chronic inflammation. Acute responses to IL-1β were lethal to SOCS3(-/Δvav) mice but not IL-6(-/-)/SOCS3(-/Δvav) mice, indicating that IL-6 was required for the lethal inflammation induced by IL-1β. Administration of IL-1β to SOCS3(-/Δvav) mice induced systemic apoptosis of lymphocytes in the thymus, spleen and lymph nodes that was dependent on the presence of IL-6. IL-6 deficiency prolonged survival of SOCS3(-/Δvav) mice and ameliorated spontaneous inflammatory disease developing during adult life. Infection of SOCS3(-/Δvav) mice with LCMV induced a lethal inflammatory response that was dependent on IL-6, despite SOCS3(-/Δvav) mice controlling viral replication. We conclude that SOCS3 is required for survival during inflammatory responses and is a critical regulator of IL-6 in vivo. |
| تدمد: | 1440-1711 0818-9641 |
| DOI: | 10.1038/icb.2011.29 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8b92bfe9a374c2b5b204d9ebf7048787 https://doi.org/10.1038/icb.2011.29 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8b92bfe9a374c2b5b204d9ebf7048787 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14401711 08189641 |
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| DOI: | 10.1038/icb.2011.29 |