Résumé
【Objective】 To explore the mechanism of macrophage-inducible C-type lectin (Mincle) and microinflammatory state in uremia. 【Methods】 SD rats were randomly divided into uremia group and sham operation group. The morphology and permeability of intestinal tissue, the morphology of intestinal tissue and macrophages were observed by transmission electron microscope, the expression of Mincle was detected in intestinal tissue sections, and the expressions of Toll-like receptor 4 (TLR-4) and NF-kappa B (NF-κB) protein on the surface of macrophages were detected by Western blotting. After the plasma was separated, the levels of endotoxin, C-reactive protein (CRP), interleulin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by Limulus lysate dynamic turbidimetric assay, and enzyme-linked immunosorbent assay (ELISA). The data were analyzed with IBM SPSS19.0 software. 【Results】 The expression of Mincle in the jejunum, ileum, and colon in uremia group was higher than that in sham-operation group (P<0.05). The expressions of TLR4 and NF-κB protein significantly differed in the ileum, jejunum and colon in uremia group (P<0.001). The levels of endotoxin, CRP, IL-6, and TNF-α were significantly increased in uremia group compared with sham-operation group (P<0.05). 【Conclusion】 In uremia, Mincle on the surface of intestinal macrophages increases and further through TLR4/NF-κB pathway mediates the transformation of intestinal macrophages to M1 type, releasing inflammatory products and causing systemic microinflammation.
Résumé
Objective To determine the expression pattern of macrophage-inducible c-type lectin (MINCLE)on Macrophage(Mφ),myeloid dendritic cell (mDC)and plasmacytoid DC(pDC)in peripheral blood (PB)and synovial fluid(SF)in patients with rheumatoid arthritis (RA).Methods For mRNA expression of MINCLE,253 RA patients and 71 healthy control subjects were enrolled.The mRNA level of MINCLE was determined by real-time PCR.For protein expression of MINCLE,18 patients with RA,5 patients with osteoarthritis(OA)and 12 healthy control subjects were enrolled.The expression of MINCLE on Mφ,mDC and pDC were detected by flow cytometry.The differences of MINCLE expressions in PB between RA patients,OA patients and healthy controls,or differences between PB and SF in RA patients were analyzed using Mann-Whitney U test or paired-samples t test.Results ①Compared to the healthy controls,RA patients showed elevated mRNA expression level of MINCLE in PBMCs[(1.65±0.36)vs (0.37±0.06),U=6057,P=2.75×10-5].②At protein level,MINCLE was hardly detected in Mφ,mDC and pDC in PB of OA patients and healthy controls.In SF,MINCLE was highiy expressed on mDC in RA patients,compared with that in OA patients[(34.8±4.4)%,U=0,P=2.6×10-3].In RA patients,the expression level of MINCLE was remarkably elevated in Mφ,mDC and pDC in SF compared with that in PB[Mφ(2.01±0.53)%vs(0.273±0.51)%,t=4.879,P=2.23×10-6;mDC(34.8±4.4)%vs(22.7±5.5)%t=2.535.P=0.017].Conclusion MINCLE is selectively expressed on Mφ.mDC and pDC in SF in RA patients.MINCLE may serve as a potential important marker,or even target,for RA and possibly even for inflammation in general.