Activation of mitogen-activated protein kinase pathways by angelan in murine macrophages

In our previous studies, we showed that angelan. a polysaccharide purified from Angelica gigas Nakai, specifically activated macrophages to induce cyt okines including inducible nitric oxide synthase (iNOS) which has strong an ti-tumor activities [Immunopharmacology, 1999; 43: 1.]. In the present stud y, we investigated the intracellular signal transduction pathways involved in the angelan-induced iNOS synthesis by murine macrophages. Protein tyrosi ne phosphorylation was induced within 5 min by angelan, and the blocking of protein tyrosine kinases (PTKs) inhibited down-stream pathways leading to iNOS production in response to angelan. Treament df RAW 264.7 cells with an gelan resulted in significant activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and p38, while stress-activated protein kinase/c-Ju n NH2 terminal kinase (SAPK/JNK) was not activated by angelan, The specific p38 inhibitor SB203580 abrogated the angelan-induced iNOS synthesis, where as the selective mitogen-activated protein kinase (MAPK)/extracellular sign ar-regulated kinase 1 (MEK-1) inhibitor PD98059 did not affect the iNOS ind uction. In conclusion, we demonstrate that PTK and p38 MAPK activation are required to transduce signals leading to iNOS expression in angelan-stimula ted murine macrophages. (C) 2001 Elsel ier Science B.V. All rights reserved .