Unknown

Dataset Information

0

Toll-Interacting Protein, Tollip, Inhibits IL-13-Mediated Pulmonary Eosinophilic Inflammation in Mice.


ABSTRACT: Toll-interacting protein (Tollip) is a key negative regulator of innate immunity by preventing excessive proinflammatory responses. Tollip genetic variation has been associated with airflow limitation in asthma subjects and Tollip expression. Whether Tollip regulates lung inflammation in a type 2 cytokine milieu (e.g., IL-13) is unclear. Our goal was to determine the in vivo role of Tollip in IL-13-mediated lung eosinophilic inflammation and the underlying mechanisms. Tollip-knockout (KO) and wild-type (WT) mice were inoculated intranasally with recombinant mouse IL-13 protein to examine lung inflammation. To determine how Tollip regulates inflammation, alveolar macrophages and bone marrow-derived macrophages from Tollip KO and WT mice were cultured with or without IL-13 and/or IL-33. IL-13-treated Tollip KO mice significantly increased lung eosinophilic inflammation and eotaxin-2 (CCL24) levels compared with the WT mice. IL-13- treated Tollip KO (vs. WT) macrophages, in the absence and particularly in the presence of IL-33, increased expression of the IL-33 receptor ST2L and CCL24, which was in part dependent on enhanced activation of interleukin (IL)-1 receptor-associated kinase 1 (IRAK1) and signal transducer and activator of transcription 6 (STAT6). Our results suggest that Tollip downregulates IL-13-mediated pulmonary eosinophilia in part through inhibiting the activity of the ST2L/IL-33/IRAK1 axis and STAT6.

SUBMITTER: Ito Y 

PROVIDER: S-EPMC5860932 | biostudies-other | 2018

REPOSITORIES: biostudies-other

altmetric image

Publications

Toll-Interacting Protein, Tollip, Inhibits IL-13-Mediated Pulmonary Eosinophilic Inflammation in Mice.

Ito Yoko Y   Schaefer Niccolette N   Sanchez Amelia A   Francisco David D   Alam Rafeul R   Martin Richard J RJ   Ledford Julie G JG   Stevenson Connor C   Jiang Di D   Li Liwu L   Kraft Monica M   Chu Hong Wei HW  

Journal of innate immunity 20180127 2


Toll-interacting protein (Tollip) is a key negative regulator of innate immunity by preventing excessive proinflammatory responses. Tollip genetic variation has been associated with airflow limitation in asthma subjects and Tollip expression. Whether Tollip regulates lung inflammation in a type 2 cytokine milieu (e.g., IL-13) is unclear. Our goal was to determine the in vivo role of Tollip in IL-13-mediated lung eosinophilic inflammation and the underlying mechanisms. Tollip-knockout (KO) and wi  ...[more]

Similar Datasets

| S-EPMC3006653 | biostudies-literature
| S-EPMC4552595 | biostudies-literature
| S-EPMC2846737 | biostudies-literature
| S-EPMC8170304 | biostudies-literature
| S-EPMC3558507 | biostudies-literature
| S-EPMC6482994 | biostudies-literature
| S-EPMC4521793 | biostudies-literature
2007-12-21 | GSE8853 | GEO
| S-EPMC7309510 | biostudies-literature
2023-12-18 | GSE238122 | GEO