Inhibition of PDE4 by apremilast attenuates skin fibrosis through directly suppressing activation of M1 and T cells

doi:10.1038/s41401-021-00656-x

	Inhibition of PDE4 by apremilast attenuates skin fibrosis through directly suppressing activation of M1 and T cells
	Lu, Qiu-kai 1,2; Fan, Chen 1; Xiang, Cai-gui 1,2; Wu, Bing 1,2; Lu, Hui-min 1,2; Feng, Chun-lan 1; Yang, Xiao-qian 1; Li, Heng 1; Tang, Wei 1,2
刊名	ACTA PHARMACOLOGICA SINICA
	2021-04-13
页码	11
关键词	PDE4 apremilast skin fibrosis macrophages
ISSN号	1671-4083
DOI	10.1038/s41401-021-00656-x
通讯作者	Li, Heng(liheng@simm.ac.cn) ; Tang, Wei(tangwei@simm.ac.cn)
英文摘要	Systemic sclerosis (SSc) is a life-threatening chronic connective tissue disease with the characteristics of skin fibrosis, vascular injury, and inflammatory infiltrations. Though inhibition of phosphodiesterase 4 (PDE4) has been turned out to be an effective strategy in suppressing inflammation through promoting the accumulation of intracellular cyclic adenosine monophosphate (cAMP), little is known about the functional modes of inhibiting PDE4 by apremilast on the process of SSc. The present research aimed to investigate the therapeutic effects and underlying mechanism of apremilast on SSc. Herein, we found that apremilast could markedly ameliorate the pathological manifestations of SSc, including skin dermal thickness, deposition of collagens, and increased expression of alpha-SMA. Further study demonstrated that apremilast suppressed the recruitment and activation of macrophages and T cells, along with the secretion of inflammatory cytokines, which accounted for the effects of apremilast on modulating the pro-fibrotic processes. Interestingly, apremilast could dose-dependently inhibit the activation of M1 and T cells in vitro through promoting the phosphorylation of CREB. In summary, our research suggested that inhibiting PDE4 by apremilast might provide a novel therapeutic option for clinical treatment of SSc patients.
资助项目	National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002-006-011] ; CAS Key Laboratory of Receptor Research[SIMM1904YKF-01] ; Science & Technology Commission of Shanghai Municipality, China[18431907100] ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020231]
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000639768200006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/296476]
专题	中国科学院上海药物研究所
通讯作者	Li, Heng; Tang, Wei
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Lab Antiinflammat & Immunopharmacol, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Sch Pharm, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Lu, Qiu-kai,Fan, Chen,Xiang, Cai-gui,et al. Inhibition of PDE4 by apremilast attenuates skin fibrosis through directly suppressing activation of M1 and T cells[J]. ACTA PHARMACOLOGICA SINICA,2021:11.
APA	Lu, Qiu-kai.,Fan, Chen.,Xiang, Cai-gui.,Wu, Bing.,Lu, Hui-min.,...&Tang, Wei.(2021).Inhibition of PDE4 by apremilast attenuates skin fibrosis through directly suppressing activation of M1 and T cells.ACTA PHARMACOLOGICA SINICA,11.
MLA	Lu, Qiu-kai,et al."Inhibition of PDE4 by apremilast attenuates skin fibrosis through directly suppressing activation of M1 and T cells".ACTA PHARMACOLOGICA SINICA (2021):11.