Tumor suppressor CYLD acts as a negative regulator for non-typeable Haemophilus influenza-induced inflammation in the middle ear and lung of mice.
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-kappaB)-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 regulator for NF-kappaB 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-kappaB activation through deubiquitinating TRAF6 and 7 and down-regulates inflammation. Our data thus indicate that CYLD acts as a negative regulator for NF-kappaB-dependent inflammation in vivo, hence protecting the host against detrimental inflammatory response to NTHi infection.
Lim
Jae Hyang
JH
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, United States of America.
Jono
Hirofumi
H
Koga
Tomoaki
T
Woo
Chang-Hoon
CH
Ishinaga
Hajime
H
Bourne
Patricia
P
Xu
Haodong
H
Ha
Un-Hwan
UH
Xu
Haidong
H
Li
Jian-Dong
JD
D000818:Animals; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D000074749:Deubiquitinating Enzyme CYLD; D004432:Ear, Middle / Q000821:virology*; D006192:Haemophilus Infections / Q000235:genetics* / Q000473:pathology*; D006193:Haemophilus influenzae / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D008168:Lung / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000378:metabolism
D016328:NF-kappa B; D048029:TNF Receptor-Associated Factor 6; C486460:TRAF7 protein, human; C486461:Traf7 protein, mouse; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; C511601:CYLD protein, mouse; D000074749:Deubiquitinating Enzyme CYLD; D003546:Cysteine Endopeptidases