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Altered response of fibroblasts from human tympanosclerotic membrane to interacting mast cells: Implication for tissue remodeling

Pawelczyk, Tadeusz, Sakowicz-Burkiewicz, Monika, Wesserling, Martyna, Grden, Marzena, Kuczkowski, Jerzy
The international journal of biochemistry & cell biology 2014 v.57 pp. 35-44
coculture, collagen, crosslinking, fibroblasts, fibrosis, functional properties, gelatinase B, histology, humans, immunoglobulin E, interleukin-6, mast cells, otitis media, pathogenesis, transforming growth factor beta 1, tumor necrosis factor-alpha
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 (FsᵀᴹS) 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-1Fᶜɛᴿᴵ) on fibroblast functional behavior. We observed that fibroblasts from normal tympanic membrane (Fsᵀᴹ) released less TNF-α, TGF-β1 and IL-6 compared to FsᵀᴹS. FsᵀᴹS but not Fsᵀᴹ upon interaction with HMC-1Fᶜɛᴿᴵ released increased quantities of TNF-α and TGF-β1. Exposing the fibroblast to HMC-1Fᶜɛᴿᴵ cells resulted in an increased synthesis of proteins including collagen. We noted that the COL2A1 transcript level increased ∼5- and ∼12-fold in Fsᵀᴹ and FsᵀᴹS co-cultured with HMC-1Fᶜɛᴿᴵ, respectively. Both Fsᵀᴹ and FsᵀᴹS upon maintenance in the primary culture released significant quantities of matrix metalloproteinase 9 (MMP-9). However, FsᵀᴹS released ∼5-fold more MMP-9 activity compared to the Fsᵀᴹ cultures. The mast cell-induced release of TNF-α, TGF-β1 and MMP-9 sustained for a longer time in FsᵀᴹS cultures compared to Fsᵀᴹ.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 FsᵀᴹS activated state could be an important factor in the pathogenesis of tympanosclerosis.