Tumor necrosis factor-α synergistically enhances polyinosinic-polycytidylic acid-induced toll-like receptor 3 signaling in cultured normal human mesangial cells: possible involvement in the pathogenesis of lupus nephritis.

Abstract

AIM:

It has been reported that tumor necrosis factor (TNF)-α plays dual controversial roles, beneficial or detrimental, in the pathogenesis of murine lupus nephritis (LN). However, its precise role in the development of human LN remains to be determined.

METHODS:

We examine the effect of pretreatment with TNF-α on the toll-like receptor 3 (TLR3) signaling induced by polyinosinic-polycytidylic acid (poly IC), a synthetic analog of viral dsRNA that makes "pseudoviral" infection in cultured normal human mesangial cells, and analyzed the expression of CC chemokine ligand 5 (CCL5) via TLR3/interferon (IFN)-β/retinoic acid-inducible gene-I (RIG-I) pathway by reverse transcriptase-polymerase chain reaction, Western blotting and enzyme-linked immunosorbent assay.

RESULTS:

We found synergistic effect of TNF-α, even at low level, on the expression of CCL5 induced by poly IC in a concentration-dependent manner, in comparison with that by poly IC alone. Knockdown of either IFN-β or RIG-I decreased CCL5 expression induced by TNF-α followed by poly IC.

CONCLUSION:

Pretreatment with TNF-α leads marked activation of the TLR3/IFN-β/RIG-I/CCL5 axis induced by "pseudoviral" infection. Since chronic local activation of proinflammatory cytokines including TNF-α in resident renal cells may exist in patients with active lupus, synergistic effect of TNF-α and "pseudoviral" infection is possibly involved in the development of LN.

• Authors: Tadaatsu Imaizumi, Tomomi Aizawa, Ryo Hayakari, Fei Xing, Pengfei Meng, Kazushi Tsuruga, Tomoh Matsumiya, Hidemi Yoshida, Liang Wang, Tetsuya Tatsuta, Hiroshi Tanaka
• Journal: Clinical and experimental nephrology (Clin Exp Nephrol) Vol. 19 Issue 1 Pg. 75-81 (Feb 2015) ISSN: 1437-7799 [Electronic] Japan
• PMID: 24627031 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokine CCL5
• Cytokines
• Receptors, Immunologic
• TLR3 protein, human
• Toll-Like Receptor 3
• Tumor Necrosis Factor-alpha
• Interferon-beta
• RIGI protein, human
• DEAD Box Protein 58
• DEAD-box RNA Helicases
• Poly I-C

Topics

• Cells, Cultured
• Chemokine CCL5 (biosynthesis)
• Cytokines (metabolism)
• DEAD Box Protein 58
• DEAD-box RNA Helicases (genetics, physiology)
• Drug Synergism
• Gene Knockdown Techniques
• Humans
• Interferon-beta (genetics, physiology)
• Lupus Nephritis (physiopathology)
• Mesangial Cells (drug effects)
• Poly I-C (pharmacology)
• Receptors, Immunologic
• Signal Transduction (drug effects)
• Toll-Like Receptor 3 (drug effects)
• Tumor Necrosis Factor-alpha (pharmacology)