PUBLICATION
IFN-γ inhibits 5-HT-induced melanin biosynthesis via downregulation of 5-HT receptors in vivo/in vitro
- Authors
- Cai, M., Zhou, L., Liao, J., Huang, Q., Xia, Z., Shang, J.
- ID
- ZDB-PUB-200403-250
- Date
- 2019
- Source
- Journal of Pharmacological Sciences 141: 1-8 (Journal)
- Registered Authors
- Shang, Jing
- Keywords
- 5-HT, 5-HT receptors, IFN-γ, Melanin biosynthesis
- MeSH Terms
-
- Animals
- Cells, Cultured
- Down-Regulation*
- Drug Discovery
- Gene Expression/drug effects
- Hypopigmentation/drug therapy
- Hypopigmentation/genetics
- In Vitro Techniques
- Interferon-gamma/pharmacology*
- Melanins/biosynthesis*
- Mice, Inbred C57BL
- Receptors, Serotonin/genetics*
- Receptors, Serotonin/metabolism*
- Serotonin/pharmacology*
- Serotonin Antagonists
- Zebrafish
- PubMed
- 31519333 Full text @ J. Pharmacol. Sci.
Citation
Cai, M., Zhou, L., Liao, J., Huang, Q., Xia, Z., Shang, J. (2019) IFN-γ inhibits 5-HT-induced melanin biosynthesis via downregulation of 5-HT receptors in vivo/in vitro. Journal of Pharmacological Sciences. 141:1-8.
Abstract
Hypopigmentation disorders, such as vitiligo, are difficult for treatment due to complicated pathogenesis, resulting from multiple factors including neural and immune elements. 5-HT and IFN-γ both play crucial roles in these skin diseases. However, the interactions between 5-HT and IFN-γ in regulation of melanogenesis is still unknown. Our study aimed at exploring whether IFN-γ affects 5-HT-induced melanogenesis and searching the mechanism. In our study, IFN-γ attenuated 5-HT-induced pigmentation and green fluorescent protein (GFP) expression in zebrafishes. In addition, we found that IFN-γ decreased serum serotonin levels as well as the cutaneous expression of tryptophan hydroxylase 1 (TPH1), 5-HT1A receptor (5-HT1AR) and 5-HT1B receptor (5-HT1BR) in C57BL/6 mice. Moreover, IFN-γ attenuated 5-HT-induced melanin biosynthesis as well as the expression of 5-HT1AR, 5-HT1BR and 5-HT2A receptor (5-HT2AR) in B16F10 cells, which blocked by interferon-γ receptor 1 and interferon-γ receptor 2 (IFNGR1/IFNGR2) antibodies. In summary, IFN-γ not only affects melanogenesis alone, but also inhibits 5-HT response on melanin biosynthesis. Mediated by IFNGR1/IFNGR2, IFN-γ downregulated 5-HT receptors expression, which directly affect 5-HT-induced melanin biosynthesis. Our work may give insights into the drug development of hypopigmentation disorders with neuro-immune derangement.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping