Abstract
Triggering receptor expressed on myeloid cells (TREM) has been broadly studied in inflammatory disease. However, the expression and function of TREM-2 remain undiscovered in acquired cholesteatoma. The expression of TREM-2 was significantly higher in human acquired cholesteatoma than in normal skin from the external auditory canal, and its expression level was positively correlated with the severity of bone destruction. Furthermore, TREM-2 was mainly expressed on dendritic cells (DCs). In human acquired cholesteatoma, the expression of proinflammatory cytokines (IL-1β, TNF-α and IL-6) and matrix metalloproteinases (MMP-2, MMP-8 and MMP-9) were up-regulated, and their expression levels were positively correlated with TREM-2 expression. Osteoclasts were activated in human acquired cholesteatoma. In an animal model, TREM-2 was up-regulated in mice with experimentally acquired cholesteatoma. TREM-2 deficiency impaired the maturation of experimentally acquired cholesteatoma and protected against bone destruction induced by experimentally acquired cholesteatoma. Additional data showed that TREM-2 up-regulated IL-1β and IL-6 expression via TLR4 instead of the TLR2 signaling pathway and promoted MMP-2 and MMP-8 secretion and osteoclast activation in experimentally acquired cholesteatoma. Therefore, TREM-2 might enhance acquired cholesteatoma-induced bone destruction by amplifying the inflammatory response via TLR4 signaling pathways and promoting MMP secretion and osteoclast activation.
Highlights
Otolaryngology Head and Neck Surgery, The third affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. *These authors contributed to this work
As a type of molecule expressed on the surface of innate immunity cells, pathogen-associated molecular pattern recognition receptors (PRRs) recognize pathogen-associated molecular patterns (PAMPs)[15]
The function of Toll-like receptors (TLRs) has been extensively studied[17,18], and the results showed that TLR4 was responsible for the inflammatory response and for osteoclast differentiation and activation via the RANK/RANKL pathway[19]
Summary
Otolaryngology Head and Neck Surgery, The third affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. *These authors contributed to this work. The function of TLRs has been extensively studied[17,18], and the results showed that TLR4 was responsible for the inflammatory response and for osteoclast differentiation and activation via the RANK/RANKL pathway[19]. This achievement provides new insight into human acquired cholesteatoma-induced bone destruction. There are no studies exploring whether TREM-2 is expressed in human acquired cholesteatoma or its association with bone destruction. The specific mechanism by which TREM-2 functions in human acquired cholesteatoma is clarified to provide a new target to inhibit human acquired cholesteatoma-induced bone destruction
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