科研之友
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摘要
Several lines of evidence suggest that a tympanosclerotic (TMS) lesion often develops secondary to acute and chronic otitis media. Histological findings indicate that fibroblasts and inflammatory cells, including mast cells, play a key role in the tympanosclerotic plaque formation. However, details on the functional characteristics of tympanosclerotic fibroblasts (Fs(Tms)) are scanty. Therefore the aim of our study was to examine the activity of human fibroblasts from tympanosclerotic lesions and to evaluate the influence of stimulated by crosslinking of IgE receptor mast cells (HMC-1(Fc epsilon RI)) on fibroblast functional behavior. We observed that fibroblasts from normal tympanic membrane (Fs(Tm)) released less TNF-alpha, TGF-beta 1 and IL-6 compared to Fs(Tms). Fs(Tms) but not Fs(Tm) upon interaction with HMC-1(Fc epsilon RI) released increased quantities of TNF-alpha and TGF-beta 1. Exposing the fibroblast to HMC-1(Fc epsilon RI) cells resulted in an increased synthesis of proteins including collagen. We noted that the COL2A1 transcript level increased similar to 5- and similar to 12-fold in Fs(Tm) and Fs(Tms) co-cultured with HMC-1(Fc epsilon RI), respectively. Both Fs(Tm) and Fs(Tms) upon maintenance in the primary culture released significant quantities of matrix metalloproteinase 9 (MMP-9). However, Fs(Tms) released similar to 5-fold more MMP-9 activity compared to the Fs(Tm) cultures. The mast cell-induced release of TNF-alpha, TGF-beta 1 and MMP-9 sustained for a longer time in Fs(Tms) cultures compared to Fs(Tm). Concluding, our data strongly indicate that increased fibroblast sensitivity to mast cell stimulation greatly contributes to the excessive fibrosis and pathological remodeling of the tympanic membrane. We postulate that the persistency of the Fs(Tms) activated state could be an important factor in the pathogenesis of tympanosclerosis.
- 出版日期2014-12
