Down-regulation of toll-like receptor 4 in the granulation tissues of postoperative mastoid cavities with otorrhea.
CONCLUSIONS
The expression of toll-like receptor (TLR) 4 and associated downstream events, such as the activation of signal pathway proteins and inflammatory cytokine production, were down-regulated in the granulation tissues of postoperative mastoid cavity with otorrhea, possibly leading to endotoxin tolerance.


OBJECTIVE
The postoperative mastoid cavity is exposed to a high density and diversity of bacteria, but very little is known about how the immune environment is maintained in these regions with otorrhea. In this study, we investigated the changes in the TLR2 and TLR4 signaling pathways and inflammatory cytokine production in the granulation tissues of mastoid cavities with otorrhea and in normal auditory canal skin.


METHODS
We investigated the expression of TLR2 and TLR4, as well as downstream signal pathway proteins, nuclear factor-kappaB (NF-kappaB) DNA binding, and secretion of tumor necrosis factor-alpha (TNF-alpha) in 28 samples of granulation tissue obtained from the postoperative mastoid cavity with otorrhea and 10 normal external auditory canal skin samples.


RESULTS
We found that the frequency of TLR2- and TLR4-positive cells was not increased in granulation tissues relative to normal skin, but the TLR4 mRNA and protein were down-regulated. In this pathophysiological process, there was also a lack of downstream signal pathway protein activation and secretion of TNF-alpha.
Xia
Ming
M
Department of Otorhinolaryngology, Qilu Hospital of Shandong University, Ji'nan, China.
Hu
Guirong
G
Zhang
Hanbing
H
Liu
Fang
F
Xu
Anting
A
D000199:Actins / Q000378:metabolism; D000328:Adult; D016022:Case-Control Studies; D002558:Cerebrospinal Fluid Otorrhea / Q000601:surgery*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D008297:Male; D008416:Mastoid / Q000473:pathology* / Q000601:surgery; D008875:Middle Aged; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000199:Actins; D020672:I-kappa B Proteins; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C507768:IRAK1 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases