Experimental evidences and signal transduction pathways involved in the activation of NF-κB/Rel by angelan in murine macrophages

In our previous studies. we showed that angelan, a polysaccharide purified from Angelica gigas Nakai, activated macrophages to induce the translocation of NF-kappa B/Rel into nucleus and DNA binding to its cognate site in the promoter of iNOS gene [Immunopharmacology 43 (1999) 1; Immunopharmacology 49 (2000) 275]. In the present study, we showed that angelan induces the transcriptional activation of NF-kappaB/Rel and investigated the intracellular signal transduction pathways involved in the angelafi-induced NF-kappaB/Rel activation by murine macrophages. Treament of RAW 264.7 cells with angelan resulted in significant activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38, while stress-activated protein kinase/c-Jun NH2 terminal kinase (SAPK/JNK) was not activated by angelan. The specific p38 inhibitor SB203580 abrogated the angelan-induced NF-kappaB/Rel activation, whereas the selective MAPK/extracellular signal-regulated kinase 1 (MEK-1) inhibitor PD98059 did not affect the NF-kappaB/Rel induction. Treatment of RAW 764.7 cells with both anti-CD14 Ab and anri-CR3 Ab significantly blocked angelan-induced NF-kappaB/Rel activation. In conclusion, we demonstrate that angelan induces NF-kappaB/Rel activation through the CD14 and CR3 membrane receptor and p38 kinase that is critically involved in the signal transduction leading to NF-kappaB/Rel activation in murine macrophages. (C) 2001 Elsevier Science B.V. All rights reserved.