@article {1363154, title = {Staphylococcus aureus activates the NLRP3 inflammasome in human and rat conjunctival goblet cells}, journal = {PLoS One}, volume = {8}, number = {9}, year = {2013}, month = {2013}, pages = {e74010}, abstract = {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.}, keywords = {Adenosine Triphosphate, Animals, Apoptosis, Carrier Proteins, Caspase 1, Conjunctiva, Cytoskeletal Proteins, Enzyme Activation, Goblet Cells, Humans, Inflammasomes, Interleukin-1beta, Male, NLR Family, Pyrin Domain-Containing 3 Protein, Rats, Receptors, Cytoplasmic and Nuclear, Receptors, Purinergic P2X4, Receptors, Purinergic P2X7, Staphylococcal Infections, Staphylococcus aureus, Toll-Like Receptor 2}, issn = {1932-6203}, doi = {10.1371/journal.pone.0074010}, author = {McGilligan, Victoria E and Gregory-Ksander, Meredith S and Li, Dayu and Moore, Jonathan E and Hodges, Robin R and Gilmore, Michael S and Moore, Tara C B and Dartt, Darlene A.} }