Effect of Mechanical Stretch on the DNCB-induced Proinflammatory Cytokine Secretion in Human Keratinocytes

Seunghee Oh,Hyungsuk Lee,Sooho Chang,Su-Hyon Lee,Seung Hyeok Seok,Hyewon Chung

doi:10.1038/s41598-019-41480-y

Seunghee Oh, Hyungsuk Lee + Show 4 more

Open Access

https://doi.org/10.1038/s41598-019-41480-y

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Abstract

Skin is exposed to various physico-chemical cues. Keratinocytes, a major component of the skin epidermis, directly interact with the surrounding extracellular matrix, and thus, biochemical and biophysical stimulations from the matrix regulate the function of keratinocytes. Although it was reported that inflammatory responses of skin were altered by an applied mechanical force, understanding how the keratinocytes sense the mechanical stimuli and regulate a cytokine secretion remains unclear. Here, we designed a device that is able to apply chemo-mechanical cues to keratinocytes and assess their proinflammatory cytokine IL-6 production. We showed that when chemical stimuli were applied with mechanical stimuli simultaneously, the IL-6 production markedly increased compared to that observed with a single stimulus. Quantitative structural analysis of cellular components revealed that the applied mechanical stretch transformed the cell morphology into an elongated shape, increased the cell size, and dictated the distribution of focal adhesion complex. Our results suggest that the mechanical cue-mediated modulation of focal adhesion proteins and actin cytoskeleton translates into intracellular signaling associated with the IL-6 production particularly in skin sensitization. Our study can be applied to understand proinflammatory responses of skin under altered biophysical environments of the skin.

Highlights

(a) A schematic of the stretchable chip mounted on the custom-built uniaxial stretch chip
The simultaneous stimuatlion of mechanical stretch and DNCB produces a synergistic effect in the inflammatory response of the skin tissue at 10% and 20% strain, and the IL-6 production vary depending on the magnitude of stretch
Despite the fact that both stimuli can affect the inflammatory response of cells and those are simultaneously present in the physiological environment of the tissue, the effects of chemical or mechanical stimuli have only been studied separately in previous studies

Summary

Introduction

(a) A schematic of the stretchable chip mounted on the custom-built uniaxial stretch chip We investigated the proinflammatory cytokine responses of human keratinocytes (HaCaTs) by treating the cells with chemicals and mechanical stretch, mimicking the physiological environment of the skin tissue.

Results

Conclusion