Cordycepin Attenuates IFN-γ-Induced Macrophage IP-10 and Mig Expressions by Inhibiting STAT1 Activity in CFA-Induced Inflammation Mice Model.

Abstract

Cordycepin, a natural derivative of adenosine, has been shown to exert pharmacological properties including anti-oxidation, antitumor, and immune regulation. It is reported that cordycepin is involved in the regulation of macrophage function. However, the effect of cordycepin on inflammatory cell infiltration in inflammation remains ambiguous. In this study, we investigated the potential role of cordycepin playing in macrophage function in CFA-induced inflammation mice model. In this model, we found that cordycepin prevented against macrophage infiltration in paw tissue and reduced interferon-γ (IFN-γ) production in both serum and paw tissue. Using luciferase reporter assay, we found that cordycepin suppressed IFN-γ-induced activators of transcription-1 (STAT1) transcriptional activity in a dose-dependent manner. Moreover, western blotting data demonstrated that cordycepin inhibited IFN-γ-induced STAT1 activation through attenuating STAT1 phosphorylation. Further investigations revealed that cordycepin inhibited the expressions of IFN-γ-inducible protein 10 (IP-10) and monokine induced by IFN-γ (Mig), which were the effector genes in IFN-γ-induced STAT1 signaling. Meanwhile, the excessive inflammatory cell infiltration in paw tissue was reduced by cordycepin. These findings demonstrate that cordycepin alleviates excessive inflammatory cell infiltration through down-regulation of macrophage IP-10 and Mig expressions via suppressing STAT1 phosphorylation. Thus, cordycepin may be a potential therapeutic approach to prevent and treat inflammation-associated diseases.

• Authors: Rirong Yang, Xiaoli Wang, Deshuang Xi, Jian Mo, Ke Wang, Shunrong Luo, Jiao Wei, Zhenghua Ren, Hui Pang, Yu Luo
• Journal: Inflammation (Inflammation) Vol. 43 Issue 2 Pg. 752-764 (Apr 2020) ISSN: 1573-2576 [Electronic] United States
• PMID: 31873836 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Chemokine CXCL10
• Chemokine CXCL9
• Cxcl10 protein, mouse
• Cxcl9 protein, mouse
• Deoxyadenosines
• STAT1 Transcription Factor
• Stat1 protein, mouse
• Interferon-gamma
• Freund's Adjuvant
• cordycepin

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Chemokine CXCL10 (antagonists & inhibitors, biosynthesis)
• Chemokine CXCL9 (antagonists & inhibitors, biosynthesis)
• Deoxyadenosines (pharmacology, therapeutic use)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Female
• Freund's Adjuvant (toxicity)
• Gene Expression
• Inflammation (chemically induced, drug therapy, metabolism)
• Interferon-gamma (toxicity)
• Macrophages (drug effects, metabolism)
• Mice
• RAW 264.7 Cells
• Random Allocation
• STAT1 Transcription Factor (antagonists & inhibitors, metabolism)