PMID- 14615068
OWN - NLM
STAT- MEDLINE
DCOM- 20040107
LR  - 20190819
IS  - 0378-4274 (Print)
IS  - 0378-4274 (Linking)
VI  - 146
IP  - 1
DP  - 2003 Dec 15
TI  - The mechanism of retinol-induced irritation and its application to anti-irritant 
      development.
PG  - 65-73
AB  - Despite many beneficial effects on dermatological applications, retinol and its 
      derivatives cause severe local irritation manifested as mild erythema and stratum 
      corneum peeling of the skin. It is hypothesized that cytokines may be important 
      inflammatory mediators in retinoid-induced dermatitis. The present study was 
      designed to determine cytokine mediators and thereby, to screen potential 
      anti-irritants in retinoid-induced inflammation. The changes in mRNA expression 
      of inflammation-related cytokines including mouse analogue of human monocyte 
      chemoattractant protein-1 (MCP-1) (JE), mouse analogue of human interleukin-8 
      (IL-8) (KC), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma 
      (IFN-gamma), IL-12p40, IL-6, IL-10, Eotaxin were determined in mouse epidermal 
      cells treated by 2% retinol using a semi-quantitative reverse 
      transcription-polymerase chain reaction (RT-PCR). The up-regulated mRNA level was 
      confirmed with protein levels in culture supernatants from human epidermal 
      keratinocytes, melanocytes, and fibroblasts treated with 10 microM retinol or 
      retinoic acid. As results, retinoid-induced inflammation was mainly mediated 
      through MCP-1 and IL-8 as evidenced by increased levels of mRNA expression and 
      protein secretion. The potential anti-irritant substances including 
      beta-sitosterol, Magnoliae flos, beta-glycyrrhetinic acid, SC-glucan, Ginko 
      extract, Raspberry extract, Schisandra extract, Cola extract, Enna complex or 
      Vegetol red grapevine extract were evaluated for their inhibitory effects on 
      retinol-induced cytokine (MCP-1 and IL-8) secretion in vitro cultured human 
      fibroblasts. Furthermore, in vivo efficacy tests for the retinol-induced 
      irritancy were performed using Draize skin irritation test in the rabbit and 
      human patch test. Most of the substances that reduced the secretion of MCP-1 and 
      IL-8 in vitro cultured fibroblasts, showed a good inhibition against the 
      retinol-induced irritation in the rabbit and human patch test. In conclusion, the 
      present study demonstrated that among proinflammatory cytokines, MCP-1 and IL-8 
      mainly mediated retinol-induced skin irritation, and that inhibition of 
      production of these cytokines can be applied as good markers to screen the 
      anti-irritants against the retinol-induced irritation.
FAU - Kim, Bae-Hwan
AU  - Kim BH
AD  - Department of Veterinary Public Health, College of Veterinary Medicine, Seoul 
      National University, San 56-1, Shillim-Dong, Kwanak-Gu, Seoul 151-742, South 
      Korea.
FAU - Lee, Yong-Soon
AU  - Lee YS
FAU - Kang, Kyung-Sun
AU  - Kang KS
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Dermatologic Agents)
RN  - 0 (Interleukin-8)
RN  - 0 (RNA, Messenger)
RN  - 11103-57-4 (Vitamin A)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/biosynthesis
MH  - Cytokines/*biosynthesis
MH  - *Dermatitis, Irritant/drug therapy/metabolism
MH  - Dermatologic Agents/*pharmacology
MH  - Female
MH  - Humans
MH  - Interleukin-8/biosynthesis
MH  - Keratinocytes/drug effects/metabolism
MH  - Melanocytes/drug effects/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - RNA, Messenger/biosynthesis
MH  - Rabbits
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Skin/*drug effects/metabolism
MH  - Vitamin A/*toxicity
EDAT- 2003/11/15 05:00
MHDA- 2004/01/08 05:00
CRDT- 2003/11/15 05:00
PHST- 2003/11/15 05:00 [pubmed]
PHST- 2004/01/08 05:00 [medline]
PHST- 2003/11/15 05:00 [entrez]
AID - S0378427403003400 [pii]
AID - 10.1016/j.toxlet.2003.09.001 [doi]
PST - ppublish
SO  - Toxicol Lett. 2003 Dec 15;146(1):65-73. doi: 10.1016/j.toxlet.2003.09.001.