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Effects of Granulocyte–Macrophage Colony-Stimulating Factor on Neuronal Senescence in Ultraviolet Irradiated Skin

Moon, Kyung-Chul, PhD; Lee, Hyun-Su, MD; Son, Seung-Tae, MD; Lee, Jae-Sun, PhD; Dhong, Eun-Sang, MD, PhD; Jeong, Seong-Ho, PhD; Han, Seung-Kyu, PhD

Journal of Craniofacial Surgery: May 2019 - Volume 30 - Issue 3 - p 930–935
doi: 10.1097/SCS.0000000000005183
Scientific Foundations

Ultraviolet (UV) irradiation affects neuronal structures of the skin and accelerates skin aging. Cytokine cascades in keratinocytes after UV irradiation may result in a paracrine inhibitory effect on nerve cells. The purpose of the present study was to determine the direct effect of cytokines induced by UV radiation on nerve cells in terms of neuronal senescence. Our group performed a preliminary study to determine cytokines induced in UV-irradiated keratinocytes. Among 40 cytokines studied, granulocyte–macrophage colony-stimulating factor (GM-CSF) was increased 4-fold in inflammation antibody array. The GM-CSF was added to cultured human neuroblastoma cells. To evaluate the effect of cellular senescence, the authors performed real-time polymerase chain reaction (RT-PCR), western blot, immunocytochemical, and phase-contrast microscopic evaluations. Expression levels of matrix metallopeptidase-9 (MMP-9), nuclear factor kappa-light-chain-enhancer of activated B cells 1 (NF-κB1), inducible nitric oxide synthase (iNOS), and interleukin β1 (IL-β1) were assessed by RT-PCR. Expression levels of AAP and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) related to formation of beta-amyloid were evaluated by western blot analysis. Expression levels of MMP-9, NF-κB1, iNOS, and IL-β1 after treatment with GM-CSF were significantly higher than those in the control group. Enhanced expression of AAP and BACE1 was also observed in the treatment group. Thus, GM-CSF might have a provocative effect on nerve cells in terms of neuronal senescence.

Department of Plastic Surgery, Korea University Guro Hospital, Seoul, South Korea.

Address correspondence and reprint requests to Eun-Sang Dhong, MD, PhD, Department of Plastic Surgery, Korea University Guro Hospital, 148 Guro-Dong, Guro-Ku, Seoul, South Korea 152-703; E-mail:

Received 19 August, 2018

Accepted 8 November, 2018

This study was supported by grant no. K1710541 from Korea University.

The authors report no conflicts of interest.

© 2019 by Mutaz B. Habal, MD.