1. IL-36α exerts pro-inflammatory effects in the lungs of mice
- Author
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Ravisankar A. Ramadas, Benjamin D. Medoff, Susan Ewart, Yoichiro Iwakura, and Ann Marie LeVine
- Subjects
CD4-Positive T-Lymphocytes ,Chemokine ,Anatomy and Physiology ,Mouse ,Pulmonology ,medicine.medical_treatment ,Interleukin-1beta ,lcsh:Medicine ,Mice ,0302 clinical medicine ,Interleukin-1alpha ,Immune Physiology ,lcsh:Science ,Cells, Cultured ,Mice, Inbred C3H ,0303 health sciences ,Multidisciplinary ,biology ,NF-kappa B ,Interleukin-36 ,Interleukin ,Animal Models ,3. Good health ,CXCL2 ,Cytokine ,Neutrophil Infiltration ,Cytokines ,Medicine ,Tumor necrosis factor alpha ,Inflammation Mediators ,Research Article ,Immunology ,Mice, Transgenic ,03 medical and health sciences ,Model Organisms ,In vivo ,Macrophages, Alveolar ,medicine ,Animals ,Biology ,Cell Proliferation ,030304 developmental biology ,Inflammation ,CD11 Antigens ,lcsh:R ,Immunity ,Pneumonia ,NFKB1 ,Mice, Inbred C57BL ,Gene Expression Regulation ,Immune System ,Cancer research ,biology.protein ,Clinical Immunology ,lcsh:Q ,Spleen ,Interleukin-1 ,030215 immunology - Abstract
Interleukin (IL-) 36 cytokines (previously designated as novel IL-1 family member cytokines; IL-1F5- IL-1F10) constitute a novel cluster of cytokines structurally and functionally similar to members of the IL-1 cytokine cluster. The effects of IL-36 cytokines in inflammatory lung disorders remains poorly understood. The current study sought to investigate the effects of IL-36α (IL-1F6) and test the hypothesis that IL-36α acts as a pro-inflammatory cytokine in the lung in vivo. Intratracheal instillation of recombinant mouse IL-36α induced neutrophil influx in the lungs of wild-type C57BL/6 mice and IL-1αβ(-/-) mice in vivo. IL-36α induced neutrophil influx was also associated with increased mRNA expression of neutrophil-specific chemokines CXCL1 and CXCL2 in the lungs of C57BL/6 and IL-1αβ(-/-) mice in vivo. In addition, intratracheal instillation of IL-36α enhanced mRNA expression of its receptor IL-36R in the lungs of C57BL/6 as well as IL-1αβ(-/-) mice in vivo. Furthermore, in vitro incubation of CD11c(+) cells with IL-36α resulted in the generation of neutrophil-specific chemokines CXCL1, CXCL2 as well as TNFα. IL-36α increased the expression of the co-stimulatory molecule CD40 and enhanced the ability of CD11c(+) cells to induce CD4(+) T cell proliferation in vitro. Furthermore, stimulation with IL-36α activated NF-κB in a mouse macrophage cell line. These results demonstrate that IL-36α acts as a pro-inflammatory cytokine in the lung without the contribution of IL-1α and IL-1β. The current study describes the pro-inflammatory effects of IL-36α in the lung, demonstrates the functional redundancy of IL-36α with other agonist cytokines in the IL-1 and IL-36 cytokine cluster, and suggests that therapeutic targeting of IL-36 cytokines could be beneficial in inflammatory lung diseases.
- Published
- 2012