IL-36α exerts pro-inflammatory effects in the lungs of mice

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 p...

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Bibliographic Details
Published in:PloS one 2012-09, Vol.7 (9), p.e45784-e45784
Main Authors: Ramadas, Ravisankar A, Ewart, Susan L, Iwakura, Yoichiro, Medoff, Benjamin D, LeVine, Ann Marie
Format: Article
Language:English
Subjects:
Animals
Antigens
Asthma
Biology
CD11 Antigens - metabolism
CD11c antigen
CD4 antigen
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - metabolism
CD4-Positive T-Lymphocytes - physiology
CD40 antigen
Cell Proliferation
Cells, Cultured
Chemokines
Clusters
Critical care
Cytokines
Cytokines - genetics
Cytokines - metabolism
Cytokines - physiology
Disease
Gene expression
Gene Expression Regulation
Hospitals
Immunology
In vivo methods and tests
Incubation
Inflammation
Inflammation Mediators - metabolism
Inflammation Mediators - physiology
Inflammatory diseases
Interleukin
Interleukin 1
Interleukin-1 - genetics
Interleukin-1 - metabolism
Interleukin-1 - physiology
Interleukin-1alpha - deficiency
Interleukin-1alpha - genetics
Interleukin-1beta - deficiency
Interleukin-1beta - genetics
Kinases
Ligands
Lung diseases
Lungs
Lymphocytes
Lymphocytes T
Macrophages
Macrophages, Alveolar - immunology
Macrophages, Alveolar - metabolism
Medicine
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Transgenic
Neutrophil Infiltration
Neutrophils
NF-kappa B - metabolism
NF-κB protein
Pathogenesis
Pneumonia - immunology
Pneumonia - metabolism
Pneumonia - pathology
Proteins
Psoriasis
Pulmonary fibrosis
Redundancy
Rodents
Spleen - immunology
Spleen - pathology
Therapeutic targets
Trachea
Tumor necrosis factor-α
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Description
Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0045784