Anti-inflammatory properties of piperlactam S: modulation of complement 5a-induced chemotaxis and inflammatory cytokines production in macrophages.
Macrophages infiltrate tissues in response to chemoattractants including complement 5a (C5a). Infiltrating macrophages clear microorganisms but also can cause tissue damage. We hypothesized that prevention of macrophages from excessive recruitment into infected sites may underlie the anti-inflammatory effects of piperlactam S, an alkaloid isolated from Piper kadsura (Choisy) Ohwi. To test this hypothesis, chemotactic migration of RAW264.7 macrophages was induced by C5a and the effects of piperlactam S were studied. The results showed that piperlactam S (1-30 microM) concentration-dependently suppressed C5a-induced migration across a fibrinogen-coated barrier with an IC50 of 4.5 +/- 0.3 microM. At 30 microM, piperlactam S inhibited chemotaxis by more than 95 % and also decreased phagocytosis by 25 % without reducing macrophage viability and adherent capacity. Furthermore, piperlactam S treated cells adhered but failed to spread and elongate as in control cells. Finally, piperlactam S inhibited the C5a-stimulated release of tumor necrosis factor-alpha and interleukin-1beta. We conclude that retardation of macrophage recruitment by interfering with the migration process and suppression of cytokines production might underlie the potential usefulness of piperlactam S as an anti-inflammatory agent.
Chiou
Wen-Fei
WF
National Research Institute of Chinese Medicine, Taipei, Taiwan, ROC. wfchiou@cma23.nricm.edu.tw
Peng
Chuen-Huei
CH
Chen
Chieh-Fu
CF
Chou
Cheng-Jen
CJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D015936:Complement C5a / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D007769:Lactams / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D031701:Piper / Q000737:chemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D007769:Lactams; C415282:piperlactam S; D015936:Complement C5a