The Expression Of TLR-2 And MMP-9 In The Epithelium Of Otitis Media Cholesteatoma

Background and ObjectOtitis media cholesteatoma is one common type of chronic suppurative otitis media. Its pathology shows high degree of proliferation of keratinizing squamous cells accumulate in the middle ear cavity, and destroy to the surrounding bone. Its clinical manifestations are discharge of ear, hearing loss, a drumming in the ears and so on. Among them, the most important clinical feature and pathophysiological processes of otitis media cholesteatoma is the osteolysis of the temporal bone. In present level of the human medicine, as long as patients are diagnosed as otitis media cholesteatoma, the surgery is the only way to prevent the development of the disease. The pathogenesis of otitis media cholesteatoma is very complex and unclarity. If the effects of the relative receptors, cytokines and various enzymes in the pathogenesis were clarity, we could formulate corresponding measures to prevent the development of the disease, such as developing and utilizing the relevant receptor antagonists, inhibitor of enzymes and so on. In the near future, drug treatment and drug prevention to otitis media cholesteatoma would be no longer out of reach. Based on the object above, the investigation on otitis media cholesteatoma is focused on the pathogenesis. Although there are varieties of pathogen theories, the exact pathogenesis is unclear yet. It is more and more interesting that TLR-2 and MMP-9 may play important roles in the pathogenesis(especially in bone destruction)of otitis media cholesteatoma .Toll-like receptors (TLRs) are a typical type of pattern recognition receptors (PRR). It is one group of receptor families closely related with the innate immune. Among TLRs family, TLR-2 is the most one to identify the pathogenic microbe types and their products.Matrix metalloproteinases (MMPs) is the general of a group of endopeptidase, which has great structural homology and many common biochemical properties. This endopeptidase can degrade the extracellular matrix. MMP-9 belongs to gelatinase.There are reports both domestic and foreign that TLR-2 and MMP-9 are over expressing in the epithelium of otitis media cholesteatoma. Therefor, we assume that they play important roles in the pathogenesis(especially in bone destruction)of otitis media cholesteatoma, and there is positive correlation between them. Endogenous ligand of TLR-2 is expressing in the tissue of otitis media cholesteatoma because of the disordering of immune system in body. This endogenous ligand activates signal transtduction of TLR-2. Then TLR-2 causes the local tissue to release a variety of proinflammatory cytokines. Some of these proinflammatory cytokines can lead to tissue damage and bone destruction, and some of these proinflammatory cytokines can up-ragulate the expressiong of MMP-9. The up-ragulation of MMP-9 results in further tissue damage and bone destruction in middle ear.Methods35 patients were chosen for experiment group, there were 21 male and 14 female, age range was from 11 to 53 years , the median age is 33, 35 specimens were collected by excision surgery, all of them were detected by common HE coloration, for ensuring that they were cholesteatoma of middle ear. 10 skin specimens of external auditory canal were collected from the myringoplasty patients as control group; they were detected by common HE coloration, for ensuring that they were normal skin of external auditory canal. All subjects were not injected or taken orally the glucocorticoid and immunosuppressor within 2 weeks. All of specimens were tested the expression of TLR-2 and MMP-9 in tissue of specimens by immunohistochemistry methods.Results1. The expression of TLR-2 was significantly increased in the endepidermis of otisits media cholesteatoma compared than the control group (p <0.001).2. The expression of MMP-9 was significantly increased in the endepidermis of otisits media cholesteatoma compared with the control group (p <0.001).3. The expression of TLR-2 is significanty associated with the expression of MMP-9 in the endepidermis of otisits media cholesteatoma (r=0.437,p <0.01). Conclusions1. TLR-2 may be playing a key role in the mechanism of bone destruction of otitis media cholesteatoma.2. MMP-9 may be playing a key role in the mechanism of bone destruction of otitis media cholesteatoma.3. There are some interactions between TLR-2 and MMP-9 in the mechanism of bone destruction of otisits media cholesteatoma.The former is possibly the induction factor to the latter.