Toll-like receptors (TLRs) are pivotal players in mediating immune responses. TLR4 is the main receptor for LPS, a strong activator of immune cells. LPS/TLR4-dependent pathway, by inducing NF-κB activation, is responsible for the release of several mediators, including IL-1β, one of the most powerful cytokines deeply involved in inflammatory and immune responses. The same pathway is also involved in NLRP3-inflammasome activation, essential for IL-1β maturation. NLRP3 is a major component of innate immune responses, being a crucial player of host immune defense against virus, bacterial, or fungal infections. NLRP3-inflammasome and IL-1β hyperactivation have been associated to the pathogenesis of a wide range of disorders and represent therapeutic targets for the development of new treatments of inflammasome driven inflammatory and autoimmune diseases. Here, we describe an in vitro protocol to induce LPS/TLR4-dependent NLRP3-inflammasome/IL-1β activation in immune cells, in order to provide a useful assay to study the efficacy of different anti inflammatory/immune-modulatory agents.
In Vitro study of TLR4-NLRP3-Inflammasome activation in Innate Immune response
Letizia Mezzasoma
;Francesca Fallarino
2023
Abstract
Toll-like receptors (TLRs) are pivotal players in mediating immune responses. TLR4 is the main receptor for LPS, a strong activator of immune cells. LPS/TLR4-dependent pathway, by inducing NF-κB activation, is responsible for the release of several mediators, including IL-1β, one of the most powerful cytokines deeply involved in inflammatory and immune responses. The same pathway is also involved in NLRP3-inflammasome activation, essential for IL-1β maturation. NLRP3 is a major component of innate immune responses, being a crucial player of host immune defense against virus, bacterial, or fungal infections. NLRP3-inflammasome and IL-1β hyperactivation have been associated to the pathogenesis of a wide range of disorders and represent therapeutic targets for the development of new treatments of inflammasome driven inflammatory and autoimmune diseases. Here, we describe an in vitro protocol to induce LPS/TLR4-dependent NLRP3-inflammasome/IL-1β activation in immune cells, in order to provide a useful assay to study the efficacy of different anti inflammatory/immune-modulatory agents.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
