Tumor Suppressor CYLD Acts as a Negative Regulator for Non-Typeable Haemophilus influenza-Induced Inflammation in the Middle Ear and Lung of Mice

Jae Hyang Lim, Hirofumi Jono, Tomoaki Koga, Chang-Hoon Woo, Hajime Ishinaga, Patricia Bourne, Haodong Xu, Un-Hwan Ha, Haidong Xu, Jian-Dong Li, Jacques Zimmer
2007 PLoS ONE  
Non-typeable Haemophilus influenza (NTHi) is an important human pathogen causing respiratory tract infections in both adults and children. NTHi infections are characterized by inflammation, which is mainly mediated by nuclear transcription factor kappaB (NF-kB)-dependent production of inflammatory mediators. The deubiquitinating enzyme cylindromatosis (CYLD), loss of which was originally reported to cause a benign human syndrome called cylindromatosis, has been identified as a key negative
more » ... ator for NF-kB in vitro. However, little is known about the role of CYLD in bacteria-induced inflammation in vivo. Here, we provided direct evidence for the negative role of CYLD in NTHi-induced inflammation of the mice in vivo. Our data demonstrated that CYLD is induced by NTHi in the middle ear and lung of mice. NTHi-induced CYLD, in turn, negatively regulates NTHi-induced NF-kB activation through deubiquitinating TRAF6 and 7 and down-regulates inflammation. Our data thus indicate that CYLD acts as a negative regulator for NF-kB-dependent inflammation in vivo, hence protecting the host against detrimental inflammatory response to NTHi infection.
doi:10.1371/journal.pone.0001032 pmid:17925880 pmcid:PMC2001183 fatcat:snawc6l36naetjvoa6t2drmhwu