ERK2-Dependent Activation of c-Jun is Required for Nontypeable H. influenzae-Induced CXCL2 Up-Regulation in Inner Ear Fibrocytes

The inner ear, composed of the cochlea and the vestibule, is a specialized sensory organ for hearing and balance. Although the inner ear has been known as an immune-privileged organ, there is emerging evidence indicating an active immune reaction of the inner ear. Inner ear inflammation can be induc...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of immunology (1950) 2012-02, Vol.188 (7), p.3496-3505
Main Authors: Oh, Sejo, Woo, Jeong-Im, Lim, David J., Moon, Sung K.
Format: Article
Language:English
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The inner ear, composed of the cochlea and the vestibule, is a specialized sensory organ for hearing and balance. Although the inner ear has been known as an immune-privileged organ, there is emerging evidence indicating an active immune reaction of the inner ear. Inner ear inflammation can be induced by the entry of pro-inflammatory molecules derived from middle ear infection. Since middle ear infection is highly prevalent in children, middle ear infection-induced inner ear inflammation can impact the normal development of language and motor coordination. Previously, we have demonstrated that the inner ear fibrocytes (spiral ligament fibrocytes) are able to recognize nontypeable Haemophilus influenzae (NTHi), a major pathogen of middle ear infection, and up-regulate a monocyte-attracting chemokine through TLR2-dependent NF-κB activation. Here, we aimed to determine molecular mechanism involved in NTHi-induced cochlear infiltration of polymorphonuclear cells. The rat spiral ligament fibrocytes (SLFs) were found to release CXCL2 in response to NTHi via activation of c-Jun, leading to the recruitment of polymorphonuclear cells to the cochlea. We also demonstrated that MEK1/ERK2 signaling pathway is required for NTHi-induced CXCL2 up-regulation in the rat SLFs. Two AP-1 motifs in the 5’-flanking region of CXCL2 appeared to function as a NTHi-responsive element, and the proximal AP-1 motif was found to have a higher binding affinity to NTHi-activated c-Jun than the distal one. Our results will enable us to better understand the molecular pathogenesis of middle ear infection-induced inner ear inflammation.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1103182