NLRP3 inflammasome mediated production of Th1/Th17 cytokines in response to inflammatory stimulants in innate immune cells

Abstract

Introduction: Monocytes play a major role in eliciting the immune response against infection. Also mast cells are found to play a critical role in mediating inflammatory immune response not only to allergic reaction but also to infection by inducing the production of inflammatory cytokines such as IL-1β, IL-6, IL-18 and IL-17. This study aims to investigate nod like receptor protein 3 (NLRP3) mediated production of Th1/Th17 cytokines in monocytes and mast cells. Materials and Methods: Mononuclear cells from peripheral and cord blood were stimulated with lipopolysaccharide (LPS), peptidoglycan (PGN) whereas human mast cell line-1 (HMC-1) cells were stimulated with histamine and LPS to analyse the activation of NLRP3 inflammosome components such as NLRP3, procaspase-1(p45), caspase-1(p10) nuclear factor-κB (NF-κB) and extracellular signal regulated kinase (ERK). The release of cytokines such as IL-1β, IL-6, IL-18 and IL-17 was quantified. Results: This study shows that stimulating the mononuclear and mast cells with LPS, PGN and LPS, histamine respectively induce the production of IL-1β, IL-6, IL-18 and IL-17 whereas the costimulation with gram positive and gram negative bacterial stimulants such as LPS and PGN showed synergistic response to cytokines whereas HMC-1 cells when stimulated with histamine produces IL-1β, IL-6 and IL-17 but when co-stimulated with LPS level of cytokines were reduced. It is mediated through activation of NLRP3 inflammosome. Also these cells utilized NFκB and ERK pathway. Conclusion: The activation of NLRP3 inflammosome in innate immune cells leads to the production of IL-1β, IL-6, IL-18 and IL-17 cytokine. The signaling pathways NF-κB and ERK are found to have been involved in the activation of NLRP3 inflammosome complex during inflammatory conditions.