Tacrolimus suppresses atopic dermatitis-associated cytokines and chemokines in monocytes

• Published in: Journal of microbiology, immunology and infection Vol. 49; no. 3; pp. 409 - 416
• Main Authors: Chang, Kai-Ting, Lin, Hugo You-Hsien, Kuo, Chang-Hung, Hung, Chih-Hsing
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01.06.2016
• Subjects: ADAM Proteins - metabolism; atopic dermatitis; Calcineurin Inhibitors - pharmacology; Cell Line; chemokine; Chemokine CCL1 - metabolism; Chemokine CCL22 - metabolism; Chemokine CXCL1 - metabolism; Chemokine CXCL10 - metabolism; cytokine; Cytokines - metabolism; Dermatitis, Atopic - drug therapy; Humans; Infectious Disease; Lipopolysaccharides; Medical Education; Monocytes - drug effects; Monocytes - metabolism; tacrolimus; Tacrolimus - pharmacology; Tumor Necrosis Factor-alpha - metabolism; Tumor Suppressor Proteins - metabolism; cytokine; atopic dermatitis; chemokine; tacrolimus
• ISSN: 1684-1182; 1995-9133
• DOI: 10.1016/j.jmii.2014.07.006

Background Calcineurin inhibitors (CNIs) exhibit remarkable efficacy in atopic dermatitis (AD). Tacrolimus, one type of CNI, is prevalently used to treat AD. AD is a chronic inflammatory disease that exhibits predominant infiltration of T-helper type 2 (Th2) cell in the acute phase and a mixed Th1 and Th0 cell pattern in chronic lesions. Cytokines such as tumor necrosis factor-α (TNF-α), Th2-related chemokines [e.g., macrophage-derived chemokine (MDC)/CCL22 and I-309/CCL1], Th1-related chemokines [e.g., interferon γ-induced protein 10 (IP-10)/CXCL10], and neutrophil chemoattractant growth-related oncogene-α (GRO-α)/CXCL1 are involved in the pathogenesis of AD. However, whether tacrolimus modulates the expression of AD-associated cytokines and chemokines remains unknown. The intracellular mechanisms of tacrolimus are also unclear. Methods Human monocytic cell line THP-1 cells were pretreated with tacrolimus and stimulated with lipopolysaccharide (LPS). The MDC, I-309, IP-10, GRO-α, and TNF-α concentrations of the cell supernatants were measured using enzyme-linked immunosorbent assay. Intracellular signaling was investigated using the Western blot analysis. Results Tacrolimus suppressed the expression of MDC, IP-10, I-309, GRO-α, and TNF-α in LPS-stimulated THP-1 cells in a dose- and time-dependent manner. All three mitogen-activated protein kinase (MAPK) inhibitors and the nuclear factor-κB inhibitor suppressed LPS-induced MDC, I-309, and TNF-α expressions in THP-1 cells. Only MAPK inhibitors suppressed LPS-induced expression of IP-10 and GRO-α. Tacrolimus suppressed the LPS-induced phosphorylation of MAPK-extracellular signal-related kinase (ERK). Conclusion Tacrolimus suppressed LPS-induced MDC, I-309, IP-10, GRO-α, and TNF-α expressions in monocytes through the MAPK-ERK pathway; thus, tacrolimus may yield therapeutic efficacy by modulating AD-associated cytokines and chemokines.