A Synthetic Peptide Derived from A1 Module in CRD4 of Human TNF Receptor-1 Inhibits Binding and Proinflammatory Effect of Human TNF-alpha

作者：Cao, Yingnan; Wang, Zhaohe; Bu, Xianzhang; Tang, Shu; Mei, Zhengrong; Liu, Peiqing^*

来源：Inflammation, 2009, 32(3): 139-145.

DOI：10.1007/s10753-009-9112-8

• inflammation
• TNF-alpha antagonist
• TNF receptor-1
• A1 module
• the fourth cystein-rich domain

Tumour necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine, which has been shown to be a causative factor in rheumatoid arthritis, inflammatory bowel disease and septic shock. Proinflammatory effect of TNF-alpha is activated mainly through human TNF receptor-1 (TNF-R1). However, the role of the fourth cystein-rich domain (CRD4) of TNF-R1 extracellular portion in the interaction of TNF-alpha with TNF-R1 is still unclear. In the present study, binding activity of TNF-alpha to TNF-R1 and protein levels of I kappa B-alpha and nuclear transcription factor kappa B (NF-kappa B) p65 subunit in HeLa cells were measured using enzyme-linked immunosorbent assay (ELISA) and western-blot analysis. Pep 3 (LRENECVS) which was derived from the hydrophilic region of A1 module in CRD4 remarkably inhibited the binding of TNF-alpha to TNF-R1, and also reversed TNF-alpha-induced degradation of I kappa B-alpha and nuclear translocation of NF-kappa B p65 subunit in HeLa cells. Our results confirmed that the hydrophilic region of A1 module in CRD4 participated in the interaction of TNF-alpha with TNF-R1, and demonstrated the potential of small-molecule TNF-alpha extracellular inhibitors targeting at A1 module in CRD4 of TNF-R1 in suppressing proinflammatory effect of TNF-alpha.

• 出版日期2009-6
• 单位中山大学