Enhancement of the release of inflammatory mediators by substance P in rat basophilic leukemia RBL-2H3 cells.
Substance P (SP), a neurotransmitter, may play an important role in neurogenic inflammation. Ginseng has been used extensively in traditional medicine; however, few studies were focused on their anti-allergic effect. Therefore, the effect and mechanism of ginsenoside Rb1 on the SP enhancement of allergic mediators were explored. In this study, SP and dinitrophenyl-bovine serum albumin (DNP-BSA) were used to activate rat basophilic leukemia (RBL)-2H3 cells. The cultured supernatants were assayed for histamine, leukotriene C(4)(LTC(4)) and interleulin-4 (IL-4) production. The mitogen-activated protein kinases (MAPKs) signaling pathway was determined by Western blotting analysis. We found that IgE/DNP-BSA, SP, ginsenoside Rb1, or MAPK specific inhibitors had no effect on cell viability and cytotoxicity. SP (30 microM) alone, did not induce histamine and LTC(4) release, but it enhanced allergen-induced histamine and LTC(4) release. In addition, SP significantly induced and enhanced allergen-activated IL-4. Ginsenoside Rb1 dose-dependently inhibited these effects. SP enhanced the allergen-activated ERK pathway in RBL-2H3 cells, and Rb1 effectively inhibited the ERK pathway activation. Although MAPK specific inhibitors suppressed LTC(4) and IL-4, only U0126 inhibited the SP enhanced histamine release. These results demonstrate that Rb1 dose-dependently inhibited SP enhanced allergen-induced mediator release and its mechanism was through the inhibition of the ERK pathway.
Liao
Ben-Ching
BC
Institute of Biomedical Science, National Chung Hsing University, Taichung, ROC.
Hou
Rolis Chien-Wei
RC
Wang
Jen-Shu
JS
Jeng
Kee-Ching G
KC
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D036145:Ginsenosides / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020078:Neurogenic Inflammation / Q000188:drug therapy*; D051381:Rats; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013373:Substance P / Q000494:pharmacology
D018926:Anti-Allergic Agents; D036145:Ginsenosides; D018836:Inflammation Mediators; D012710:Serum Albumin, Bovine; D013373:Substance P; C089027:ginsenoside Rb1, malonyl