11694459

pubmed:Citation

4

Interleukin (IL)-13 is a central mediator of the processes underlying the induction of airways hyperreactivity (AHR) in the allergic lung. However, the mechanisms by which IL-13 induces AHR and the associated role of inflammatory infiltrates as effector cells has not been fully elucidated. In this investigation, we show that intratracheal administration of IL-13 induces AHR in the presence and absence of inflammation. The initial AHR response (peak, 6 to 24 h; preinflammatory phase [PIP]) was dissociated from inflammation (eosinophilia) and mucus hypersecretion but was critically regulated by signaling through the IL-4 receptor alpha chain (IL-4Ralpha) and signal transducers and activators of transcription (STAT)-6. The second response (> 24 h, inflammatory phase [IP]) was characterized by an amplified AHR, eosinophil accumulation, and mucus hypersecretion. These features of the IP were not observed in IL-4Ralpha- or STAT-6-deficient mice. To determine the role of eosinophils in the induction of IP AHR and mucus hypersecretion, we administered IL-13 to IL-5-, eotaxin-, and IL-5/eotaxin- deficient mice. IL-13-mediated eosinophil accumulation was significantly attenuated (but not ablated) in IL-5-, eotaxin-, or IL-5/eotaxin-deficient mice. However, IL-13-induced AHR and mucus secretion occurred independently of IL-5 and/or eotaxin. These findings demonstrate that IL-13 can induce AHR independently of these eosinophil regulatory cytokines and mucus hypersecretion. Furthermore, IL-13-induced AHR, eosinophilia, and mucus production are critically dependent on the IL-4Ralpha chain and STAT-6.

eng

IM

MEDLINE

1044-1549

Print

NLM

522-30

pubmed-meshheading:11694459-Animals, pubmed-meshheading:11694459-Bronchial Hyperreactivity, pubmed-meshheading:11694459-Bronchoconstrictor Agents, pubmed-meshheading:11694459-Chemokine CCL11, pubmed-meshheading:11694459-Chemokines, CC, pubmed-meshheading:11694459-Eosinophils, pubmed-meshheading:11694459-Interleukin-13, pubmed-meshheading:11694459-Interleukin-4, pubmed-meshheading:11694459-Interleukin-5, pubmed-meshheading:11694459-Intubation, Intratracheal, pubmed-meshheading:11694459-Male, pubmed-meshheading:11694459-Methacholine Chloride, pubmed-meshheading:11694459-Mice, pubmed-meshheading:11694459-Mice, Inbred BALB C, pubmed-meshheading:11694459-Mice, Mutant Strains, pubmed-meshheading:11694459-Mucus, pubmed-meshheading:11694459-Muscle, Smooth, pubmed-meshheading:11694459-Receptors, Interleukin-4, pubmed-meshheading:11694459-STAT6 Transcription Factor, pubmed-meshheading:11694459-Trans-Activators

Interleukin-13 mediates airways hyperreactivity through the IL-4 receptor-alpha chain and STAT-6 independently of IL-5 and eotaxin.

Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't