Experimental evidences and signal transduction pathways involved in the activation of NF-kappa B/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 translocatio n 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 tr anscriptional activation of NF-kappaB/Rel and investigated the intracellula r signal transduction pathways involved in the angelafi-induced NF-kappaB/R el activation by murine macrophages. Treament of RAW 264.7 cells with angel an resulted in significant activation of extracellular signal-regulated kin ases 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 p 38 inhibitor SB203580 abrogated the angelan-induced NF-kappaB/Rel activatio n, 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 blo cked angelan-induced NF-kappaB/Rel activation. In conclusion, we demonstrat e that angelan induces NF-kappaB/Rel activation through the CD14 and CR3 me mbrane receptor and p38 kinase that is critically involved in the signal tr ansduction leading to NF-kappaB/Rel activation in murine macrophages. (C) 2 001 Elsevier Science B.V. All rights reserved.