Treatment with TNF-α inhibitor rectifies M1 macrophage polarization from blood CD14+ monocytes in patients with psoriasis independent of STAT1 and IRF-1 activation. Issue 3 (September 2018)

• Record Type: Journal Article
• Authors: Lin, Shang-Hung; Chuang, Hung-Yi; Ho, Ji-Chen; Lee, Chih-Hung; Hsiao, Chang-Chun
• Is Part Of: Journal of dermatological science. Volume 91:Issue 3(2018)
• Page Start: 276
• Page End: 284
• Publication Date: 2018-09
• Subjects: TNF-α tumor necrosis factor alpha -- CD14 cluster of differentiation 14 -- STAT1 signal transducer and activator of transcription 1 -- IRF-1 Interferon regulatory factor 1; Psoriasis -- Macrophage polarization -- TNF-α inhibitor -- STAT1 -- IRF-1; Dermatology -- Periodicals; Skin Diseases -- Periodicals; Dermatologie -- Périodiques; 616.5005
• DOI: 10.1016/j.jdermsci.2018.05.009
• Languages: English
• ISSNs: 0923-1811

Abstract

Abstract: Background: Psoriasis is a systemic inflammatory disease with dramatic responses to TNF-α inhibitors. TNF-α is mainly produced by macrophages. However, how macrophage polarization contributes to psoriasis remains unknown. Objective: We aimed to investigate the molecular mechanisms of macrophage polarization in psoriasis. Methods: 8 patients with moderate to severe psoriasis (Male/Female: 4/4, average age: 47.9 years old) and 8 healthy controls (Male/Female: 4/4, average age: 49.3 years old) were recruited. Their peripheral CD14+ monocytes were isolated with magnetic beads and then were differentiated into macrophages. The differential macrophage polarization was compared among normal controls, psoriatic patients before and after TNF-α inhibitors. The U937 cells were used to investigate the mechanisms by which TNF-α altered the macrophage polarization. Results: The ratio of M1 to M2a macrophage polarization was higher in psoriatic patients comparing with that in controls. The decreasing M1/M2a ratio was parallel to decreasing PASI severity score after adalimumab treatment. Consistently, TNF-α blockage decreased M1/M2a ratio in U937 cells. The induction of STAT1 and IRF-1 in polarized U937 M1 cells was inhibited by TNF-α inhibitor. However, STAT1 and/or IRF-1 interference could not resume M1 polarization. In skin, the increased M1 and M2 infiltration in lesions returned to baseline after successful treatment with TNF-α inhibitor. Conclusions: Increased M1 polarization is associated with higher disease severity in psoriasis, resuming to baseline after successful treatment by TNF-α inhibitors. TNF-α blockage inhibits M1 polarization through STAT1- and IRF-1-independent pathways. Macrophage polarization may contribute to disease progression in psoriasis.