Abstract
IL-33 modulates both innate and adaptive immune responses at tissue sites including lung and may play critical roles in inflammatory lung disease. Although IL-33 expression can be altered upon NF-Kappa B activation, here we examine regulation by Oncostatin M, a gp130 cytokine family member, in mouse lung tissue. Responses were assessed in BALB/c mouse lung at day 7 of transient overexpression using endotracheally administered adenovirus encoding OSM (AdOSM) or empty vector (AdDel70). Whole lung extracts showed induction of IL-33 mRNA (>20-fold) and protein (10-fold increase in immunoblots) by AdOSM relative to AdDel70. Immunohistochemistry for IL-33 indicated a marked induction of nuclear staining in alveolar epithelial cells in vivo. Oncostatin M stimulated IL-33 mRNA and IL-33 full length protein in C10 mouse type 2 alveolar epithelial cells in culture in time-dependent and dose-dependent fashion, whereas IL-6, LIF, IL-31, IL-4, or IL-13 did not, and TGFβ repressed IL-33. IL-33 induction was associated with activation of STAT3, and pharmacological inhibition of STAT3 ameliorated IL-33 levels. These results indicate Oncostatin M as a potent inducer of IL-33 in mouse lung epithelial cells and suggest that an OSM/IL-33 axis may participate in innate immunity and inflammatory conditions in lung.
Highlights
Recent evidence supports important functions of the cytokine IL-33 in both innate and adaptive immune responses
To determine whether IL33 is expressed and/or regulated in this system, we examined both protein and mRNA levels in mice treated with control AdDel70 vector or adenovirus encoding OSM (AdOSM) vector (Figure 1)
The antibody detected prominent bands corresponding to full length IL-33, whereas mature IL-33 signal was absent/low in mouse lung extracts of both AdDel70- and AdOSM-treated BALB/c mice
Summary
Recent evidence supports important functions of the cytokine IL-33 in both innate and adaptive immune responses. IL-33 showed ability to induce T helper 2 cytokines and subsequent work has further characterized IL-33 biology and roles in homeostasis and disease including bacterial and helminthic infection, allergy and chronic inflammation of lung, joint, skin, CNS, and cardiovascular tissues (as reviewed by others [5,6,7,8]). The extracellular soluble form of IL-33 interacts with its receptor complex composed of ST2 and IL-1RAP [9] and induces the NF-Kappa B and MAP kinase cell signaling pathways [3]. Less is known about the roles of IL33 within the nucleus; cellular IL-33 is associated with heterochromatin [11] and can modulate NF-Kappa B signaling [12]
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