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Inflammation

, Volume 35, Issue 3, pp 935–943 | Cite as

Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (TWEAK) Mediates p38 Mitogen-Activated Protein Kinase Activation and Signal Transduction in Peripheral Blood Mononuclear Cells from Patients with Lupus Nephritis

  • Liu Zhi-Chun
  • Zhou Qiao-Ling
  • Liu Zhi-Qin
  • Li Xiao-Zhao
  • Zuo Xiao-xia
  • Tang Rong
Article

Abstract

Forty-two patients with systemic lupus erythematosus (SLE), including 26 patients with renal damage and 16 without, and 20 healthy controls were included in the study. The isolated peripheral blood mononuclear cells (PBMCs) were treated with a p38 inhibitor (SB203580) or anti-tumor necrosis factor-like weak inducer of apoptosis (TWEAK) mAb, with or without phytohemagglutinin/phorbol myristate acetate (PHA/PMA) stimulation. Western blot experiments were used to evaluate the protein expression of TWEAK and p38 MAPK in PBMCs .Next, the contents of interleukin-10 (IL-10) and monocyte chemoattractant protein-1 (MCP-1) in the supernatant were measured by ELISA. The results showed that expression of TWEAK protein in PBMCs from lupus nephritis patients was significantly higher than that from SLE patients without renal damage and healthy controls. PHA/PMA simulation could upregulate the productions of TWEAK and p-p38MAPK in PBMCs from patients with SLE. Anti-TWEAK mAb treatment downregulated both TWEAK and p-p38 MAPK expression in PBMCs, as well as IL-10 and MCP-1 in the supernatant; SB203580 had the same effect on cytokine production in PBMC, but had no effect on the expression of TWEAK. Our results suggested that TWEAK–p38 MAPK–IL-10, MCP-1 signaling pathway in PBMC played an important pathogenic role in lupus nephritis.

KEY WORDS

TWEAK lupus nephritis IL-10 MCP-1 p38 MAPK 

Abbreviations

DAPI

4′,6-Diamidino-2-phenylindole

SLE

Systemic lupus erythematosus

LN

Lupus nephritis

TWEAK

Tumor necrosis factor-like weak inducer of apoptosis

p38 MAPK

P38 mitogen- activated protein kinase

IL-10

Interleukin-10

MCP-1

Monocyte chemoattractant protein-1

TNFRSF

Tumor Necrosis Factor receptor superfamily

NRSLE

SLE patients without renal involvement

PBMC

Peripheral blood mononuclear cell

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Liu Zhi-Chun
    • 1
  • Zhou Qiao-Ling
    • 2
  • Liu Zhi-Qin
    • 3
  • Li Xiao-Zhao
    • 2
  • Zuo Xiao-xia
    • 4
  • Tang Rong
    • 2
  1. 1.Department of Rheumatology and ImmunologyThe Second Affiliated Hospital of Suzhou UniversitySuzhouChina
  2. 2.Department of Nephrology, Xiangya HospitalCentral South UniversityChangshaPeople’s Republic of China
  3. 3.Department of Biological Science & EngineeringHebei Technology UniversityShijiazhuangChina
  4. 4.Department of Rheumatology and Immunology, Xiangya HospitalCentral South UniversityChangshaChina

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