Long-wave Ultraviolet Ray Promotes Inflammation in Keloid-derived Fibroblasts by Activating P38-NFκB1 Signaling Pathway

Abstract

Abstract One of the main mechanisms of keloid formation is the persistent chronic inflammation, which initiates the activation of keloid-derived fibroblasts (KFs) and boosts the production of extracellular matrix. Meanwhile, 95% of the ultraviolet rays that reach the earth are long-wave ultraviolet (UVA). However, the effect of UVA on keloids is currently unclear. The objective of our research is to investigate UVA’s impact on keloids. Cell viability assay, migration assay, and cell cycle analysis were conducted. UVA’s impacts on gene expressions were detected by real-time quantitative polymerase chain reaction, western blot analysis, enzyme-linked immunosorbent assay, and immunofluorescence. Our results indicated that UVA inhibited the proliferation and migration of KFs. In addition, after UVA irradiation, the expressions of matrix metallopeptidase 1 and matrix metallopeptidase 2 markedly increased in KFs. Moreover, the expression of α-smooth muscle actin and collagen I decreased. Furthermore, KFs with UVA irradiation secreted more interleukin-6 and interleukin-8 in the culture medium. And it was confirmed that the protein expressions of inflammation-related factors, including P38, CK2A, NFκB1, and P65, increased observably in KFs with UVA irradiation. The protein expression of IKBα, also known as NFκB inhibitor α, decreased. All these observations suggested that UVA irradiation could inhibit cellular activity and collagen production in KFs while promoting inflammation by activating P38-NFκB1 signal pathway.