PMID- 31420628 OWN - NLM STAT- MEDLINE DCOM- 20190822 LR - 20200917 IS - 1671-167X (Print) IS - 1671-167X (Linking) VI - 51 IP - 4 DP - 2019 Aug 18 TI - [Altered serum cytokine expression profile in systemic sclerosis and its regulatory mechanisms]. PG - 716-722 LID - 10.19723/j.issn.1671-167X.2019.04.021 [doi] AB - OBJECTIVE: To analyze the expression profile of serum cytokines in patients with systemic sclerosis (SSc) and explore its possible regulatory mechanisms. METHODS: Serum and DNA of peripheral blood mononuclear cells were collected from 30 SSc patients and 80 normal controls (NCs). According to the presence or absence of interstitial lung disease (ILD) in SSc, the patients were divided into SSc with ILD group and SSc without ILD group. According to the degree of skin involvement, the patients were divided into diffuse systemic scleroderma (dcSSc) group and limited systemic scleroderma (lcSSc) group. According to the presence of anti-topoisomerase-1 antibody (anti-Scl-70 antibody) in the serum of patients with SSc, they were divided into SSc Scl-70 (+) group and SSc Scl-70 (-) group. 27 cytokines in serum were detected by Luminex MAGPIX detection system and Bio-Plex Pro Human Cytokine 27-plex Assay kit: interleukin-1beta (IL-1beta), interleukin-1 receptor antagonist (IL-1ra), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12P70, IL-13, IL-15, IL-17, basic fiber growth factor (BASIC FGF), eotaxin, granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), interferon-gamma (IFN-gamma), interferon-gamma induced protein 10(IP-10), monocyte chemotactic protein 1(MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha), macrophage inflammatory protein 1beta(MIP-1beta), platelet-derived growth factor BB (PDGF-BB), regulated on activation in normal T-cell expressed and secreted (RANTES), tumor necrosis factor-alpha (TNF-alpha), and vascular endothelial growth factor(VEGF). Methylation sites were detected by Illumina 450K methylation chip. RESULTS: Compared with NCs group, the expression of 12 cytokines (BASIC FGF, eotaxin, G-CSF, GM-CSF, IFN-gamma, IL-1beta, IL-1ra, IL-6, IP-10, MCP-1, TNF-alpha and RANTES) in the SSc group significantly increased (P<0.05), IL-5 was decreased expression in the SSc group (P<0.05), there was no significant difference in the expressions of the other 14 cytokines. Compared with lcSSc group, 9 cytokines (eotaxin, IL-5, MCP-1, IL-2, RANTES, IL17A, IL-8, MIP-1beta and PDGF-BB) increased in dcSSc group, but there was no significant difference. Compared with SSc without ILD group, IL-15 increased in SSC with ILD group [18.2 (172.97) ng/L vs. 2.03(0.05) ng/L, P<0.05]. Compared with SSc Scl-70 (-) group, the expression of IP-10 decreased in SSc Scl-70 (+) group [1 030 (2 196.6) ng/L vs. 1 878 (2 964) ng/L, P<0.05]. The correlation analysis of serum cytokines with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) showed that IL-6 was positively correlated with ESR (r =0.04, P= 0.017), MCP-1 (r=0.49, P=0.043) and MIP-1beta (r=0.41, P=0.007) positively correlated with CRP. By analyzing the changes of methylation sites of cytokines, it was found that cg17744604 in IL-10 TSS1500 region, cg06111286 in IL-12P70 TSS200 region, cg07935264 in IL-1beta TSS200 region, cg01467417 in IL-1ra TSS1500 region, cg03989987 in IL-1ra 5'UTR region and cg21099624 in VEGF TSS200 region were all hypomethylated. CONCLUSION: There were different cytokines expression profiles in the serum of SSc patients, and the altered cytokines were correlected with the degree of skin damage and pulmonary fibrosis. Many cytokines were regulated by methylation. FAU - Zhu, H L AU - Zhu HL AD - Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha 410008, China. FAU - DU, Q AU - DU Q AD - Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha 410008, China. FAU - Chen, W L AU - Chen WL AD - Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha 410008, China. FAU - Zuo, X X AU - Zuo XX AD - Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha 410008, China. FAU - Li, Q Z AU - Li QZ AD - Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha 410008, China. FAU - Liu, S J AU - Liu SJ AD - Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha 410008, China. LA - chi PT - Journal Article PL - China TA - Beijing Da Xue Xue Bao Yi Xue Ban JT - Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences JID - 101125284 RN - 0 (Cytokines) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Vascular Endothelial Growth Factor A) SB - IM MH - Cytokines MH - Humans MH - *Leukocytes, Mononuclear MH - *Scleroderma, Systemic MH - Tumor Necrosis Factor-alpha MH - Vascular Endothelial Growth Factor A PMC - PMC7433485 EDAT- 2019/08/20 06:00 MHDA- 2019/08/23 06:00 PMCR- 2019/08/18 CRDT- 2019/08/18 06:00 PHST- 2019/08/18 06:00 [entrez] PHST- 2019/08/20 06:00 [pubmed] PHST- 2019/08/23 06:00 [medline] PHST- 2019/08/18 00:00 [pmc-release] AID - bjdxxbyxb-51-4-716 [pii] AID - 10.19723/j.issn.1671-167X.2019.04.021 [doi] PST - ppublish SO - Beijing Da Xue Xue Bao Yi Xue Ban. 2019 Aug 18;51(4):716-722. doi: 10.19723/j.issn.1671-167X.2019.04.021.