Die Rolle von Fibroblasten bei chronischer Rhinosinusitis: Einfluss auf Entzündung und Gewebereparatur

Introduction: Fibroblasts are a key cell population in connective tissue, involved in extracellular matrix (ECM) synthesis, cytokine/growth factor secretion, and wound healing regulation. These functions are crucial for tissue homeostasis and inflammatory regulation. By this means fibroblasts influence the course of inflammation and the chronification of the disease process and contribute to architecture and morphology in nasal tissue.

Methods: Fibroblast cultures from polyp tissue (SPDF) and chronically inflamed nasal mucosa (NSDF) were established to investigate cellular differences in fibroblasts from chronic rhinosinusitis with (CRSwNP) and without (CRSsNP) nasal polyps. Wound healing, migration, and their response to Th2 cytokines IL-4/IL-13 with and without competing antibody for the corresponding receptors were analyzed by gene expression assays.

Results: NSDFs exhibited 2.7-fold greater migration and higher wound closure vs. SPDFs. IL-4/IL-13 upregulated matricellular POSTN, chemokines (CCL11, CCL26), ECM proteins (COL1A, fibronectin) in SPDFs, with only moderate and non reproducible changes in NSDFs. The competing antibody was able to reduce this cytokine-induced gene expression in SPDFs.

Discussion: The results suggest SPDFs have limited tissue repair ability. This functional changes observed in vitro might be induced by the in vivo inflammation, promoting chronic damage further enhancing inflammation in CRSwNP. SPDFs also displayed stronger Th2 pro-inflammatory and matrix deposition in responses to Th2 cytokines. This increased sensitivity may accelerate CRSwNP pathogenesis. These results highlight the importance of disrupting Th2 signaling in CRSwNP to prevent inflammatory and remodeling processes in CRSwNP by fibroblasts.

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