Differential Roles of Cystathionine Gamma-Lyase and Mercaptopyruvate Sulfurtransferase in Hapten-Induced Colitis and Contact Dermatitis in Mice

Hydrogen sulfide (H S) has been shown to act as both anti-inflammatory and pro-inflammatory mediators. Application of H S donors generally protects against inflammation; however, experimental results using mice lacking endogenous H S-producing enzymes, such as cystathionine γ-lyase (CTH) and mercapt...

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Veröffentlicht in:International journal of molecular sciences 2023-01, Vol.24 (3), p.2659
Hauptverfasser: Akahoshi, Noriyuki, Hasegawa, Ryoka, Yamamoto, Shingo, Takemoto, Rintaro, Yoshizawa, Toshiki, Kamichatani, Waka, Ishii, Isao
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Sprache:eng
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Zusammenfassung:Hydrogen sulfide (H S) has been shown to act as both anti-inflammatory and pro-inflammatory mediators. Application of H S donors generally protects against inflammation; however, experimental results using mice lacking endogenous H S-producing enzymes, such as cystathionine γ-lyase (CTH) and mercaptopyruvate sulfurtransferase (MPST), are often contradictory. We herein examined two types of model hapten-induced inflammation models, colitis (an inflammatory bowel disease model of mucosal immunity) and contact dermatitis (a type IV allergic model of systemic immunity), in CTH-deficient ( ) and MPST-deficient ( ) mice. Both mice exhibited no significant alteration from wild-type mice in trinitrobenzene sulfonic acid (Th1-type hapten)-induced colitis (a Crohn's disease model) and oxazolone (Th1/Th2 mix-type; Th2 dominant)-induced colitis (an ulcerative colitis model). However, (not ) mice displayed more exacerbated phenotypes in trinitrochlorobenzene (TNCB; Th1-type)-induced contact dermatitis, but not oxazolone, at the delayed phase (24 h post-administration) of inflammation. CTH mRNA expression was upregulated in the TNCB-treated ears of both wild-type and mice. Although mRNA expression of pro-inflammatory cytokines (IL-1β and IL-6) was upregulated in both early (2 h) and delayed phases of TNCB-triggered dermatitis in all genotypes, that of Th2 (IL-4) and Treg cytokines (IL-10) was upregulated only in mice, when that of Th1 cytokines (IFNγ and IL-2) was upregulated in wild-type and mice at the delayed phase. These results suggest that (upregulated) CTH or H S produced by it helps maintain Th1/Th2 balance to protect against contact dermatitis.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms24032659