IκBNS induces Muc5ac expression in epithelial cells and causes airway hyper-responsiveness in murine asthma models
| Autor: | Masaya Yokota, Kiyoshi Takeda, Koichi Hirose, Yusuke Yokoyama, Kotaro Suzuki, Hiroaki Takatori, Hiroshi Nakajima, Tomohiro Tamachi, Yuko Maezawa, Akira Suto |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Goblet cell Immunology Mucin Pattern recognition receptor Context (language use) respiratory system Biology NFKBID respiratory tract diseases 03 medical and health sciences Haematopoiesis 030104 developmental biology medicine.anatomical_structure Immune system medicine Immunology and Allergy Bone marrow |
| Zdroj: | Allergy. 72:1043-1053 |
| ISSN: | 0105-4538 |
| DOI: | 10.1111/all.13079 |
| Popis: | Background In allergic asthma, environmental allergens including house dust mite (HDM) trigger pattern recognition receptors and activate downstream signaling pathways including NF-κB pathways not only in immune cells but also in airway epithelial cells. Recent studies have shown that NF-κB activation is regulated positively or negatively depending on the cellular context by IκBNS (encoded by the gene Nfkbid), one of atypical IκB proteins, in the nucleus. Therefore, we hypothesized that IκBNS expressed in immune cells or epithelial cells is involved in the regulation of asthmatic responses. Aim To determine the roles of IκBNS in HDM-induced asthmatic responses. Methods Roles of IκBNS in HDM-induced airway inflammation and airway hyper-responsiveness (AHR) were examined by using IκBNS-deficient (Nfkbid−/−) mice. Roles of IκBNS expressed in hematopoietic cells and nonhematopoietic cells were separately evaluated by bone marrow chimeric mice. Roles of IκBNS expressed in murine tracheal epithelial cells (mTECs) were examined by air–liquid interface culture. Results House dust mite-induced airway inflammation and AHR were exacerbated in mice lacking IκBNS in hematopoietic cells. In contrast, HDM-induced airway inflammation was exacerbated, but AHR was attenuated in mice lacking IκBNS in nonhematopoietic cells. The induction of Muc5ac, a representative mucin in asthmatic airways, was reduced in Nfkbid−/− mTEC, whereas the induction of Spdef, a master regulator of goblet cell metaplasia, was not impaired in Nfkbid−/− mTEC. Moreover, IκBNS bound to and activated the MUC5AC distal promoter in epithelial cells. Conclusion IκBNS is involved in inducing Muc5ac expression in lung epithelial cells and causing AHR in HDM-induced asthma models. |
| Databáze: | OpenAIRE |
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