Temporal expression patterns of distinct cytokines and M1/M2 macrophage polarization regulate rheumatoid arthritis progression.

Kung, Chia-Chi; Dai, Shih-Ping; Chiang, Hao; Huang, Hsu-Shan; Sun, Wei-Hsin

Kung, Chia-Chi; Dai, Shih-Ping; Chiang, Hao; Huang, Hsu-Shan; Sun, Wei-Hsin.

Afiliación

Kung CC; Department of Life Sciences, Zhongli District, National Central University, Taoyuan City, Taiwan.
Dai SP; Division of Anesthesiology, Fu Jen Catholic University Hospital, New Taipei City, Taiwan.
Chiang H; School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
Huang HS; Department of Life Sciences, Zhongli District, National Central University, Taoyuan City, Taiwan.
Sun WH; Department of Life Sciences, Zhongli District, National Central University, Taoyuan City, Taiwan.

Mol Biol Rep ; 47(5): 3423-3437, 2020 May.

Article en En | MEDLINE | ID: mdl-32277445

RESUMEN

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of synovial joints and often associated with chronic pain. Chronic joint inflammation is attributed to severe proliferation of synoviocytes and resident macrophages and infiltration of immune cells. These cells secrete pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and IL-17 to overcome actions of anti-inflammatory cytokines, thereby maintaining chronic inflammation and pain. The imbalance between pro-inflammatory cytokines (produced by M1 macrophages) and anti-inflammatory cytokines (produced by M2 macrophages) is a feature of RA progression, but the switch time of M1/M2 polarization and which receptor regulates the switch remain unsolved. Here we used an established RA mouse model to demonstrate that TNF-α expression was responsible for the initial acute stage of inflammation and pain (1-4 weeks), IL-17 expression the transition stage (4-12 weeks), and IL-6 expression the later maintenance stage (> 12 weeks). The switch time of M1/M2 polarization occurred at 4-8 weeks. We also identified a potential compound, anthra[2,1-c][1,2,5] thiadiazole-6,11-dione (NSC745885), that specifically inhibited T-cell death-associated gene 8 (TDAG8) function and expression. NSC745885 decreased joint inflammation and destruction and attenuated pain by reducing cytokine production and regulating the M1/M2 polarization switch. TDAG8 may participate in regulating the M1/M2 polarization and temporal expression of distinct cytokines to control RA progression.

Asunto(s)

Artritis Reumatoide/inmunología; Citocinas/genética; Macrófagos/metabolismo; Animales; Antiinflamatorios/farmacología; Artritis Reumatoide/metabolismo; Artritis Reumatoide/patología; Células Cultivadas; Citocinas/metabolismo; Expresión Génica/genética; Inflamación/metabolismo; Interleucina-17/metabolismo; Interleucina-6/metabolismo; Masculino; Ratones; Ratones Endogámicos ICR; Dolor/genética; Dolor/metabolismo; Sinoviocitos/metabolismo; Transcriptoma/genética; Factor de Necrosis Tumoral alfa/genética; Factor de Necrosis Tumoral alfa/metabolismo

Palabras clave

Chronic pain; IL-17; IL-6; M1 macrophages; M2 macrophages; Rheumatoid arthritis; TDAG8; TNF-α

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Reumatoide / Citocinas / Macrófagos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Mol Biol Rep Año: 2020 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Países Bajos

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