Friction-Induced Inflammation

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Friction-induced inflammation is a new hypothesis that implicates interfacial shear stress as a trigger for the production of pro-inflammatory signals, which in severe cases may lead to chronic inflammation and pain. If frictional shear stresses at the interface exceed physiological norms, a likely cellular response may involve the release of pro-inflammatory signals (e.g., proteins, cytokines, chemokines, and enzymes). Ocular lubricity and comfort are critically dependent on the stability of the tear film and the health of the corneal and conjunctival epithelium. The insertion of a contact lens may increase contact pressures and shear stresses on the epithelia, but these are difficult to measure in vivo. Epithelial cells are known to sense and respond to mechanical strains and deformations through a process called mechanotransduction. The effects of frictional shear stress on cellular responses were experimentally measured in vitro by sliding soft, spherical shell hydrogel probes against human corneal epithelial (hTCEpi) cell monolayers with two different normal forces: 500 and 1000 µN, giving ~ 30 and ~ 60 Pa shear stresses, respectively. Molecular biology assays (quantitative reverse transcription—polymerase chain reaction, RT-qPCR, and enzyme-linked immunosorbent assay, ELISA) followed friction experiments. Compared to control populations, RT-qPCR revealed frictional shear stresses of 60 Pa were sufficient to increase gene expression of the pro-inflammatory genes Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Matrix Metalloproteinase 9 (MMP9), and pro-apoptotic genes DNA Damage-Inducible Transcript 3 (DDIT3) and FAS Cell Surface Death Receptor (FAS). An ELISA of growth media sampled after sliding revealed IL-6 cytokine release increased by 100% following shear stress experiments. These results suggest that frictional shear stress may be at least partly responsible for inducing inflammatory responses in corneal epithelial cells in vitro.