Photodermatol Photoimmunol Photomed. 2018;34:145–151. wileyonlinelibrary.com/journal/phpp
© 2017 John Wiley & Sons A/S.
Published by John Wiley & Sons Ltd
Accepted: 12 October 2017
Repeated ultraviolet irradiation induces the expression of
Toll- like receptor 4, IL- 6, and IL- 10 in neonatal human
Hee Jin Song | Si Hyub Lee | Gwang Seong Choi | Jeonghyun Shin
Department of Dermatology, Inha University
School of Medicine, Incheon, Korea
Jeonghyun Shin, M.D., Ph.D., Department
of Dermatology, Inha University School of
Medicine, Incheon, Korea.
Ministry of Health & Welfare, Republic of
Korea, Grant/Award Number: A110777
Background: Human melanocytes express Toll- like receptor 4 (TLR4), which regulates
ultraviolet (UV)- induced cutaneous immunosuppression in Langerhans cells.
Lipopolysaccharide (LPS) stimulation increases melanocyte pigmentation and TLR4
expression, while inducing local innate inflammatory responses.
Aims: We investigated whether UV radiation induces TLR4 expression in neonatal
human melanocytes (NHMs) and how this affects the immune system.
Methods: We cultured NHMs with LPS treatment or with one- time or repeated UVA
or UVB exposure, and investigated and compared the effects on TLR4 expression,
melanin contents, and cytokine production.
Results: NHMs in the resting state did not express TLR4. LPS stimulation induced
TLR4 expression and increased pigmentation. TLR4 expression was not detected after
single- dose UVA or UVB treatment, but pigmentation increased. Repeated UV treat-
ment induced TLR4 expression and increased pigmentation. LPS stimulation and re-
peated UV treatment increased IL- 6 secretion, and repeated UVB treatment increased
IL- 10 secretion.
Conclusion: These results suggest that human melanocytes may actively participate in
UV- induced immune modulation.
innate immunity, melanocytes, toll-like receptor 4, ultraviolet radiation
1 | INTRODUCTION
Human melanocytes produce melanin, a pigment that protects the skin
against damage from ultraviolet (UV) radiation. While pigment produc-
tion is their main function, melanocytes also play roles in the skin’s
immune response and in cellular secretion.
Within the innate immune
system, pathogen identification is mediated by pattern- recognition re-
ceptors, such as the Toll- like receptors (TLRs). These receptors trans-
duce signals that lead to NF- κB activation, subsequently inducing the
expressions of several pro- inflammatory cytokines and chemokines.
In humans, over 10 TLRs recognize distinct microbial ligands.
The skin acts as a permeable physical barrier to external environ-
mental stressors, playing an important role as the first defense against
cutaneous microbial invasion. Many studies report TLRs expression
and functions in keratinocytes.
Human melanocytes are known to
express TLR2, TLR3, TLR4, TLR7, and TLR9, but their functions are not
Human melanocytes also express the functionally ac-
tive lipopolysaccharide (LPS) receptor proteins TLR4 and CD14.
studies have mainly focused on the roles of TLRs in melanogenesis.
Upon activation, the TLR2 and TLR4 pathways increase pigmentation
and activate TLR5, while the TLR7 pathway decreases pigmentation in
The effects of ultraviolet (UV) radiation on skin include increased
pigmentation, inflammation, immunosuppression, and carcinogene-
Upon exposure to UV radiation, melanocytes respond through
paracrine factors that activate melanogenesis as well as the DNA