Suppressive effect of topically applied CX-659S, a novel diaminouracil derivative, on the contact hypersensitivity reaction in various animal models

Yuso Goto, Yoshifumi Inoue, Masami Tsuchiya, Masakazu Isobe, Takamasa Ueno, Uchi Hiroshi, Masutaka Furue, Hideya Hayashi

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: The T-cell-mediated contact hypersensitivity reaction (CHR) is thought to be involved in the pathogenesis of clinical cutaneous disorders including atopic dermatitis. A novel diaminouracil derivative, CX-659S, has been reported to have an inhibitory activity against picryl chloride (PC)-induced CHR when administered either orally or percutaneously. The inhibitory effect of topical CX-659S was assessed in three CHR models in the present study. In addition, to elucidate the mechanism of action of this compound, we examined the effect of CX-659S on the expression of messenger RNAs for proinflammatory cytokines after elicitation in PC models. Methods: For the in vivo evaluation of the efficacy of CX-659S, we used PC- or oxazolone-induced CHR in mice and 2,4-dinitrochlorobenzene (DNCB)-induced CHR in guinea pigs. CX-659S was topically applied immediately after the hapten challenge in each model. To assess the effect on gene expression of cytokines, we used the reverse transcriptase-polymerase chain reaction (RT-PCR), a semiquantitative technique with specific primers. Results: Topical CX-659S dose-dependently inhibited ear swelling at 24 h after the challenge in the two mouse models. This inhibitory effect was histologically confirmed in the PC model. Topically applied CX-659S also inhibited erythema and edema formation 24 h after challenge in the guinea pig model. CX-659S inhibited the expression of mRNA for proinflammatory cytokines IL-1β and TNF-α in vivo. Conclusions: Topically applied CX-659S showed significant inhibitory activities against CHR models both in mice and in guinea pigs. Inhibition profiles of CX-659S toward mRNA expression for proinflammatory cytokines corroborated these findings. CX-659S thus could be a useful therapeutic agent for allergic cutaneous disorders such as allergic contact dermatitis and atopic dermatitis.

Original languageEnglish
Pages (from-to)341-348
Number of pages8
JournalInternational Archives of Allergy and Immunology
Volume123
Issue number4
DOIs
Publication statusPublished - Dec 1 2000

Fingerprint

Contact Dermatitis
Animal Models
Picryl Chloride
Cytokines
Guinea Pigs
Atopic Dermatitis
Messenger RNA
CX 659S
Oxazolone
Dinitrochlorobenzene
Skin
Allergic Contact Dermatitis
Haptens
Erythema
Reverse Transcriptase Polymerase Chain Reaction
Interleukin-1
Ear
Edema
T-Lymphocytes
Gene Expression

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Suppressive effect of topically applied CX-659S, a novel diaminouracil derivative, on the contact hypersensitivity reaction in various animal models. / Goto, Yuso; Inoue, Yoshifumi; Tsuchiya, Masami; Isobe, Masakazu; Ueno, Takamasa; Hiroshi, Uchi; Furue, Masutaka; Hayashi, Hideya.

In: International Archives of Allergy and Immunology, Vol. 123, No. 4, 01.12.2000, p. 341-348.

Research output: Contribution to journalArticle

Goto, Yuso ; Inoue, Yoshifumi ; Tsuchiya, Masami ; Isobe, Masakazu ; Ueno, Takamasa ; Hiroshi, Uchi ; Furue, Masutaka ; Hayashi, Hideya. / Suppressive effect of topically applied CX-659S, a novel diaminouracil derivative, on the contact hypersensitivity reaction in various animal models. In: International Archives of Allergy and Immunology. 2000 ; Vol. 123, No. 4. pp. 341-348.
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AU - Furue, Masutaka

AU - Hayashi, Hideya

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AB - Background: The T-cell-mediated contact hypersensitivity reaction (CHR) is thought to be involved in the pathogenesis of clinical cutaneous disorders including atopic dermatitis. A novel diaminouracil derivative, CX-659S, has been reported to have an inhibitory activity against picryl chloride (PC)-induced CHR when administered either orally or percutaneously. The inhibitory effect of topical CX-659S was assessed in three CHR models in the present study. In addition, to elucidate the mechanism of action of this compound, we examined the effect of CX-659S on the expression of messenger RNAs for proinflammatory cytokines after elicitation in PC models. Methods: For the in vivo evaluation of the efficacy of CX-659S, we used PC- or oxazolone-induced CHR in mice and 2,4-dinitrochlorobenzene (DNCB)-induced CHR in guinea pigs. CX-659S was topically applied immediately after the hapten challenge in each model. To assess the effect on gene expression of cytokines, we used the reverse transcriptase-polymerase chain reaction (RT-PCR), a semiquantitative technique with specific primers. Results: Topical CX-659S dose-dependently inhibited ear swelling at 24 h after the challenge in the two mouse models. This inhibitory effect was histologically confirmed in the PC model. Topically applied CX-659S also inhibited erythema and edema formation 24 h after challenge in the guinea pig model. CX-659S inhibited the expression of mRNA for proinflammatory cytokines IL-1β and TNF-α in vivo. Conclusions: Topically applied CX-659S showed significant inhibitory activities against CHR models both in mice and in guinea pigs. Inhibition profiles of CX-659S toward mRNA expression for proinflammatory cytokines corroborated these findings. CX-659S thus could be a useful therapeutic agent for allergic cutaneous disorders such as allergic contact dermatitis and atopic dermatitis.

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