%0 Journal Article %J PLoS One %D 2013 %T Staphylococcus aureus activates the NLRP3 inflammasome in human and rat conjunctival goblet cells %A McGilligan, Victoria E %A Gregory-Ksander, Meredith S %A Li, Dayu %A Moore, Jonathan E %A Hodges, Robin R %A Gilmore, Michael S %A Moore, Tara C B %A Dartt, Darlene A. %K Adenosine Triphosphate %K Animals %K Apoptosis %K Carrier Proteins %K Caspase 1 %K Conjunctiva %K Cytoskeletal Proteins %K Enzyme Activation %K Goblet Cells %K Humans %K Inflammasomes %K Interleukin-1beta %K Male %K NLR Family, Pyrin Domain-Containing 3 Protein %K Rats %K Receptors, Cytoplasmic and Nuclear %K Receptors, Purinergic P2X4 %K Receptors, Purinergic P2X7 %K Staphylococcal Infections %K Staphylococcus aureus %K Toll-Like Receptor 2 %X The conjunctiva is a moist mucosal membrane that is constantly exposed to an array of potential pathogens and triggers of inflammation. The NACHT, leucine rich repeat (LRR), and pyrin domain-containing protein 3 (NLRP3) is a Nod-like receptor that can sense pathogens or other triggers, and is highly expressed in wet mucosal membranes. NLRP3 is a member of the multi-protein complex termed the NLRP3 inflammasome that activates the caspase 1 pathway, inducing the secretion of biologically active IL-1β, a major initiator and promoter of inflammation. The purpose of this study was to: (1) determine whether NLRP3 is expressed in the conjunctiva and (2) determine whether goblet cells specifically contribute to innate mediated inflammation via secretion of IL-1β. We report that the receptors known to be involved in the priming and activation of the NLRP3 inflammasome, the purinergic receptors P2X4 and P2X7 and the bacterial Toll-like receptor 2 are present and functional in conjunctival goblet cells. Toxin-containing Staphylococcus aureus (S. aureus), which activates the NLRP3 inflammasome, increased the expression of the inflammasome proteins NLRP3, ASC and pro- and mature caspase 1 in conjunctival goblet cells. The biologically active form of IL-1β was detected in goblet cell culture supernatants in response to S. aureus, which was reduced when the cells were treated with the caspase 1 inhibitor Z-YVAD. We conclude that the NLRP3 inflammasome components are present in conjunctival goblet cells. The NRLP3 inflammasome appears to be activated in conjunctival goblet cells by toxin-containing S. aureus via the caspase 1 pathway to secrete mature IL1-β. Thus goblet cells contribute to the innate immune response in the conjunctiva by activation of the NLRP3 inflammasome. %B PLoS One %V 8 %P e74010 %8 2013 %G eng %N 9 %1 http://www.ncbi.nlm.nih.gov/pubmed/24040145?dopt=Abstract %R 10.1371/journal.pone.0074010