Article Text
Abstract
Objectives To analyze the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in muscle tissue from patients with polymyositis/dermatomyositis (PM/DM) and the effects of TRAIL on apoptosis of human skeletal muscle cells. To analyze the correlated clinical significance by testing the serum tumor necrosis factor–related apoptosis-inducing ligand (sTRAIL) level of patients with polymyositis/dermatomyositis.
Methods Muscle biopsy samples and blood samples were selected from 40 PM/DM patients and 20 healthy volunteers. The expression of TRAIL in the muscle tissue was detected by immunohistochemistry. The human skeletal muscle cells were treated with different concentrations of TRAIL (0, 1, 5, 10, 50 ng/mL) in primary culture. The apoptotic rates of primary cultured human skeletal muscle cells were measured by flow cytometry. The level of serum TRAIL was tested by enzyme-linked immunosorbent assay (ELISA).
Results The expression of TRAIL was found in muscle tissue samples from the PM/DM patients and healthy controls. The expression of TRAIL in the muscle tissue from the PM/DM patients was significantly higher than those from healthy controls (P<0.05).
The skeletal muscle cells from PM/DM patients had significantly higher apoptosis rate (%) than healthy volunteers. After 24 hours stimulated by different concentration of TRAIL (0, 1, 5, 10, 50 ng/mL), the apoptosis rate (%) in PM/DM group are:13.72±11.52, 31.23±14.05, 40.09±9.15, 39.91±13.38, 31.32±9.07,respectively.The apoptosis rates in PM/DM group are significantly higher than in control group in same stimulated concentration of TRAIL (P<0.05). And the 5ng/mL stimulated concentration made the highest apoptosis rate.
The serum level of sTRAIL in PM/DM patients was 1380.71±126.49 ng/L, which significantly higher than healthy control group's 493.89±33.32 ng/L (P<0.05). And the serum levels of sTRAIL in PM/DM patients with dysphagia was 1775.76±321.95 ng/L, which was significantly higher than 958.24±155.66 ng/L (P<0.05) from patients without dysphagia. There were no differences between sTRAIL from patients with or without interstitial lung disease (P>0.05). The serum levels of sTRAIL in Jo-1 positive group was 562.36±52.99 ng/L, which was significantly lower than in Jo-1 negative group's 1334.57±181.21 ng/L (P<0.05). Spearman rank correlation analysis showed that level of sTRAIL was negatively correlated with lactic dehydrogenase (LDH) (r=-4.03, P<0.05).
Conclusions TRAIL plays a important role in pathogenesis of polymyositis/dermatomyositis and its abnormal expression is closely related to PM/DM patients' clinical features.
Disclosure of Interest None declared
DOI 10.1136/annrheumdis-2014-eular.2643