Jiaguang Su1, Yanbin Pan2, WenJun Zheng1,*
1Department of Dermatology, the first affiliated hospital of Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, Guangxi, China - 2Department of Dermatology, the third affiliated hospital of Guangxi Medical University, 13 Dancun Road, Nanning 530031, Guangxi, People’s Republic of China
Purpose: To investigate the mechanism involved in FC-99-induced alleviation of lupus nephritis (LN) in MRL/lpr lupus mice.
Methods: Mice were divided into FC-99 group given intraperitoneal injection of FC-99, LN group, and normal control group (NC group) with an equivalent volume of normal saline. The injection lasted for 20 weeks. Mice urine was collected weekly from week 9. Urine protein content, renal pathological changes, relative expression levels of tumor necrosis factor-α (TNF-α), as well as mono- cyte chemoattractant protein (MCP-1) and interleukin-6 (IL-6) mRNA were determined with urine protein ELSA kit, H & E staining, and RT-PCR, respectively. The dendritic cells (DCs) were divided into control group (no treatment), lipopolysaccharide group (100 ng/ml LPS daily) and FC-99 group (50 μmol FC-99 for 120 min, and 100 ng/ml LPS daily). The expression levels of major histocom- patibility complex II (MHCII), CD40, CD80 and CD86 were determined using flow cytometry; while the expressions of interleukin-1 receptor-associated kinase 4 (IRAK4), phospho-interleukin-1 receptor-associated kinase 4 (P-IRAK4), p38 and phosphorylated p38 (P-p38) by were determined with western blot.
Purpose: To investigate the mechanism involved in FC-99-induced alleviation of lupus nephritis (LN) in MRL/lpr lupus mice.
Results: The urine protein content of the 3 groups ranked in a descending order was: LN group > FC-99 group > NC group (p<0.05). There were no obvious renal pathological changes in the NC group, but there were glomerular sclerosis, tubule-intersti- tial fibrosis, tubular atrophy, glomerular leukocyte infiltration and tubule-interstitial mononuclear cell infiltration in the FC-99 and LN groups. However, the lesions were milder in the FC-99 group than in the LN group. Relative expressions of TNF-α, MCP-1 and IL-6 mRNA in the kidney tissues of FC-99 group and NC group were significantly lower than those in the LN group (p<0.05). The expression levels of MHCII, CD40, CD80 and CD86 in DCs of control and FC-99 groups were significantly lower than those in the LPS group (p<0.05). Relative expressions of P-IRAK4 and P-p38 protein in 3 groups were in the order LPS group > FC-99 group > control group (p<0.05).
Conclusion: Inhibition of LPS-induced activation of the MAPK pathway in DCs is involved in the alleviation of LN in MRL/lpr lupus mice by FC-99.
FC-99, DCs, MAPK pathway, LN.
10.19193/0393-6384_2019_2_164