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

• 作者: Qiu-kai Lu Chen Fan Cai-gui Xiang Bing Wu Hui-min Lu Chun-Ian Feng Xiao-qian Yang Heng Li Wei Tang
• 来源期刊: 中国药理学报（英文版）
• 年，卷（期）: 2022,（2）
• 所属期刊栏目: Inflammation and Immunopharmacology
• 页码范围: 376-386
• 页数: 11页
• 语种: 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 α-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.