Protective effect of ixerisoside A against UVB-induced pro-inflammatory cytokine production in human keratinocytes.
Human skin is the first line of defense for the protection of the internal organs of the body from different stimuli. Ultraviolet B (UVB), one of the harmful radiations for skin, is widely known to induce abnormally increased cytokine release from keratinocytes leading to inflammatory skin disorders. IL-6 and IL-8 induce an acute-phase response and stimulate leukocyte infiltration in the skin. Previous studies have shown that chronic exposure to UVB radiation increases cyclooxygenase-2 (COX‑2) expression through various cell signaling pathways, resulting in skin cancer. Recent studies have shown that the activation of extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 MAPK is strongly correlated with acute inflammation and development of skin cancer caused by an increased expression of COX-2. Ixerisoside A (IXA) is an active constituent of Ixeris dentata of the Compositae (Asteraceae) family. The effect of IXA on skin inflammation has yet to be elucidated. To determine the anti-inflammatory effects of IXA, we examined its effect on UVB-induced pro-inflammatory cytokine production in human keratinocytes (HaCaT cells) by observing these cells in the presence or absence of IXA. In this study, pro-inflammatory cytokine production was determined by enzyme-linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (rt-pcr), and western blot analysis to evaluate the activation of mitogen-activated protein kinases (MAPKs). IXA inhibited UVB-induced production of the pro-inflammatory cytokines IL-6 and IL-8 in a dose-dependent manner. Moreover, IXA inhibited the expression of COX-2, ERK, JNK, and p38 MAPKs, indicating that the secretion of the pro-inflammatory cytokines IL-6 and IL-8, and COX-2 expression was inhibited by blocking MAPK phosphorylation. These results indicated that IXA potentially protects against UVB-induced skin inflammation.
BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570‑749, Republic of Korea.
Sung-Bae
SB
Kim
Department of Oriental Pharmacy, College of Pharmacy and Wonkwang‑Oriental Medicines Research Institute, Institute of Biotechnology, Wonkwang University, Iksan, Jeonbuk 570‑749, Republic of Korea.
Ji-Eun
JE
Kim
Department of Oriental Pharmacy, College of Pharmacy and Wonkwang‑Oriental Medicines Research Institute, Institute of Biotechnology, Wonkwang University, Iksan, Jeonbuk 570‑749, Republic of Korea.
Ok-Hwa
OH
Kang
BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570‑749, Republic of Korea.
Su-Hyun
SH
Mun
Department of Oriental Pharmacy, College of Pharmacy and Wonkwang‑Oriental Medicines Research Institute, Institute of Biotechnology, Wonkwang University, Iksan, Jeonbuk 570‑749, Republic of Korea.
Yun-Soo
YS
Seo
BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570‑749, Republic of Korea.
Da-Hye
DH
Kang
BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570‑749, Republic of Korea.
Da-Wun
DW
Yang
Korea Research Institute of Chemical Technology, Daejeon 305‑600, Republic of Korea.
Shi-Yong
SY
Ryu
Department of Oriental Pharmacy, College of Pharmacy and Wonkwang‑Oriental Medicines Research Institute, Institute of Biotechnology, Wonkwang University, Iksan, Jeonbuk 570‑749, Republic of Korea.
Young-Mi
YM
Lee
Department of Oriental Pharmacy, College of Pharmacy and Wonkwang‑Oriental Medicines Research Institute, Institute of Biotechnology, Wonkwang University, Iksan, Jeonbuk 570‑749, Republic of Korea.
Dong-Yeul
DY
Kwon
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism* / Q000528:radiation effects; D007783:Lactones / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D020011:Protective Agents / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000494:pharmacology*; D014466:Ultraviolet Rays
D016207:Cytokines; D018836:Inflammation Mediators; D007783:Lactones; D010936:Plant Extracts; D020011:Protective Agents; D012717:Sesquiterpenes; C562105:ixerisoside A; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases