Immunosuppressive activity of capsaicinoids: capsiate derived from sweet peppers inhibits NF-kappaB activation and is a potent antiinflammatory compound in vivo.
Capsiate and its dihydroderivatives are the major capsaicinoids of sweet pepper. These new capsaicinoids do not activate the vanilloid receptor type 1 (VR1) but they share with capsaicin (CPS)some biological activities mediated in a VR1-independent fashion. In this study we show that CPS and nordihydrocapsiate (CPT) inhibit early and late events in T cell activation, including CD69, CD25 and ICAM-1 cell surface expression, progression to the S phase of the cell cycle and proliferation in response to TCR and CD28 co-engagement. Moreover, both CPS and CPT inhibit NF-kappaB activation in response to different agents including TNF-alpha. CPS itself does not affect the DNA-binding ability of NF-kappaB but it prevents IkappaB kinase activation and IkappaBalpha degradation in a dose-dependent manner, without inhibiting the activation of the mitogen-activated protein kinases, p38, extracellular regulated kinase and c-Jun N-terminal protein kinase. Moreover, intraperitoneal pretreatment with CPT prevented mice from lethal septic shock induced by lipopolysaccharide. In a second model of inflammation CPT pretreatment greatly reduced the extensive damage in the glandular epithelium observed in the bowel of DSS-treated mice. Taken together, these results suggest that CPT and related synthetic analogues target specific pathways involved in inflammation, and hold considerable potential for dietary health benefits as well as for pharmaceutical development.
Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Córdoba, Spain.
Rocío
R
Sancho
Concepción
C
Lucena
Antonio
A
Macho
Marco A
MA
Calzado
Magdalena
M
Blanco-Molina
Alberto
A
Minassi
Giovanni
G
Appendino
Eduardo
E
Muñoz
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology*; D002212:Capsicum / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D015533:Transcriptional Activation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D007166:Immunosuppressive Agents; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D000072000:NF-KappaB Inhibitor alpha; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D002211:Capsaicin