Biosketch / Results /
Michael PillingerProfessor, Department of Medicine;Professor, Department of Biochemistry and Molecular Pharmacology
227 East 30th Street
New York, NY 10016
Research SummaryIn rheumatoid arthritis (RA) the tissues of the involved joints assume inflammatory, autoimmune and pseudoneoplastic features. The cells contributing to these phenotypes include neutrophils, which accumulate in the RA joint space, and synovial fibroblasts (SFs), which proliferate in great numbers in the RA synovium (pannus) and secrete matrix metalloproteinases (MMPs) that participate in the destruction of cartilage.
The mitogen-activated protein kinases (MAPKs) include the Erks, Jnks and p38. Our laboratory is interested in the role of MAPKs on neutrophils and SF regulation. We are especially interested in the role of Erks. We have observed that, in neutrophils, Erk is rapidly activated in response to chemoattractants and regulates neutrophil adhesion, a critical early step in the acute inflammation. In SFs we have shown that Erk regulates proliferation, but also the release of some (MMP-1,3,9) but not other (MMP-13) metalloproteinases. Interestingly, high-dose salicylates (doses achievable in patients but in excess of those needed to inhibit cyclooxygenase) inhibit Erk in both neutrophils and SFs, and concordantly inhibit neutrophil adhesion and SF MMP release. Non-salicylate nonsteroidals also inhibit cyclooxygenase but do not reproduce these effects. Indeed, COX inhibition actually leads to enhancement of MMP release from synovial fibroblasts.
Our present aims are threefold: 1) to understand the mechanisms through which Erk positively regulates neutrophil adhesion; 2) to understand the cross talk between prostaglandin production and Erk activation in SF responses; 3) to understand the mechanisms through which salicylates inhibit Erk, as a clue into how Erk, and other signaling pathways, may be pharmacologically targeted. A better understanding of these phenomena may lead to new approaches, and new agents, for the treatment of RA.}
Research InterestsSignal transduction and the regulation of cells involved in inflammation and rheumatoid arthritis
Presence of gout is associated with increased prevalence and severity of knee osteoarthritis among older men: results of a pilot study
Howard, Rennie G; Samuels, Jonathan; Gyftopoulos, Soterios; Krasnokutsky, Svetlana; Leung, Joseph; Swearingen, Christopher J; Pillinger, Michael H
2015-03-01; 1076-1608,Journal of clinical rheumatology. JCR - id: 1473722, year: 2015 Journal Article
Inpatient Gout: A Review
Fisher, Mark C; Pillinger, Michael H; Keenan, Robert T
2014-10-13; 1523-3774,Current rheumatology reports - id: 1300242, year: 2014 JOURNAL ARTICLE
The causes of drug-induced muscle toxicity
Jones, Jonathan D; Kirsch, Hannah L; Wortmann, Robert L; Pillinger, Michael H
2014-09-11; 1040-8711,Current opinion in rheumatology - id: 1181132, year: 2014 JOURNAL ARTICLE
Hyperuricemia, Gout, and Related Comorbidities: Cause and Effect on a Two-Way Street
Karis, Elaine; Crittenden, Daria B; Pillinger, Michael H
2014-06-20; 0038-4348,Southern medical journal - id: 1036702, year: 2014 REVIEW
Comparative Cardiovascular (CV) Risk and Outcomes Among Patients with Gout, Osteoarthritis (OA), or Both.
Krasnokutsky, Svetlana; Keenan, Robert T; Schneck, Laura; Tenner, Craig; Strauss, Helene; Crittenden, Daria; Lehmann, Aaron; Pillinger, Michael H
2015-01-29; 2326-5205,Arthritis & rheumatology - id: 1443932, year: 2014