Interleukin-17和肿瘤坏死因子表现出功能层次结构，以调节来自银屑病患者的单核细胞中的基质金属蛋白酶的产生。
Interleukin-17 and Tumor Necrosis Factor Show a Functional Hierarchy to Regulate the Production of Matrix Metalloproteases by Monocytes from Patients with Psoriasis.
发表日期：2023 Mar
作者：
Rashidi Springall, Maria Fernanda Ortega-Springall, Ana Elena Guerrero-Ponce, María Elisa Vega-Memije, Luis M Amezcua-Guerra
来源：
Cellular & Molecular Immunology
摘要：
白细胞介素-17（IL-17）和肿瘤坏死因子（TNF）通过基质金属蛋白酶（MMP）调节组织重塑。目前尚不清楚这些细胞因子在牛皮癣中是否具有功能层次。牛皮癣受试者（n = 60）的血清TNF（1,403对1,058pg / mL），IL-17（1,528对820pg / mL），MMP-1（1,999对1,039pg / mL）和MMP-9（1,950对1,561pg / mL）水平均高于对照组（n = 60）水平。MMP抑制物（TIMP-1; 1,374与1,218pg / mL）降低了牛皮癣受试者的水平。血清IL-17与MMP-2（rs = 0.40）和TIMP-1（rs = -0.26）水平相关。未刺激的单核细胞MMP-1、MMP-2和MMP-9的产生在牛皮癣受试者中较高，而TIMP-1产生较低。TNF刺激增加了所有MMP，而TIMP-1产生保持不变。IL-17刺激增加了所有MMP，而TIMP-1产生在牛皮癣患者中降低。相比于TNF，IL-17刺激后单核细胞中MMP-9的产生更高。在牛皮癣细胞中，与TNF相比，IL-17的TIMP-1产生下降程度更大。与TNF刺激相比，牛皮癣受试者中的MMP-1 / TIMP-1、MMP-2 / TIMP-1和MMP-9 / TIMP-1比例在IL-17刺激后更高；在对照组中，仅MMP-2 / TIMP-1比例出现同样情况。支持IL-17阻断作为切除性牛皮癣的一线治疗，因为它比TNF更具有调节MMPs / TIMP-1平衡的能力。
Interleukin-17 (IL-17) and tumor necrosis factor (TNF) regulate tissue remodeling through matrix metalloproteinases (MMPs). It is not yet clear whether these cytokines have a functional hierarchy in psoriasis. Serum levels of TNF (1,403 versus 1,058 pg/mL), IL-17 (1,528 versus 820 pg/mL), MMP-1 (1,999 versus 1,039 pg/mL), and MMP-9 (1,950 versus 1,561 pg/mL) were higher in psoriasis subjects (n = 60) than in control subjects (n = 60). Tissue inhibitor of MMPs (TIMP-1; 1,374 versus 1,218 pg/mL) was lower in psoriasis subjects. Serum IL-17 was correlated with MMP-2 (rs = 0.40) and TIMP-1 (rs = -0.26) levels. Unstimulated production of MMP-1, MMP-2, and MMP-9 by monocytes was higher in psoriasis subjects, whereas TIMP-1 production was lower. TNF stimulation increased all MMPs, whereas TIMP-1 production was unchanged. IL-17 stimulation increased all MMPs, whereas TIMP-1 production was decreased in psoriasis subjects. MMP-9 production was higher in monocytes stimulated with IL-17 compared with TNF. TIMP-1 production was decreased more by IL-17 than by TNF, but only in psoriasis cells. MMP-1/TIMP-1, MMP-2/TIMP-1, and MMP-9/TIMP-1 ratios were higher after IL-17 stimulation (compared with TNF stimulation) in psoriasis subjects; this occurred in controls only for the MMP-2/TIMP-1 ratio. IL-17 has a greater ability than TNF to dysregulate the MMPs/TIMP-1 balance, supporting IL-17 blockade as first-line treatment in cutaneous psoriasis.