Michael H. Pillinger

Michael H. Pillinger

Chief of Rheumatology, VA NY Harbor Health Care System

Director, Clinical and Translational Science Institute Education and Careers Unit

Director, Rheumatology Fellowship Program

Professor, Department of Medicine

Professor, Department of Biochemistry and Molecular Pharmacology

Keywords
signal transduction and the regulation of cells involved in inflammation and rheumatoid arthritis
Summary

In 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.}

These focus areas and their associated publications are derived from medical subject headings from PubMed.
represents one publication
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Professor, Department of Medicine

Professor, Department of Biochemistry and Molecular Pharmacology

Chief of Rheumatology, VA NY Harbor Health Care System

Director, Clinical and Translational Science Institute Education and Careers Unit

Director, Rheumatology Fellowship Program

Thottam, Gabrielle E; Krasnokutsky, Svetlana; Pillinger, Michael H

Current rheumatology reports. 2017 Aug 26; 19(10):60-60

Slobodnick, A; Krasnokutsky, S; Lehmann, R A; Keenan, R T; Quach, J; Francois, F; Pillinger, M H

Scandinavian journal of rheumatology. 2017 Jun 26; 1-2

Modjinou, Dodji V; Krasnokutsky, Svetlana; Gyftopoulos, Soterios; Pike, Virginia C; Karis, Elaine; Keenan, Robert T; Lee, Kristen; Crittenden, Daria B; Samuels, Jonathan; Pillinger, Michael H

Clinical rheumatology. 2017 Jun 16; ?-?

Krasnokutsky, Svetlana; Oshinsky, Charles; Attur, Mukundan; Ma, Sisi; Zhou, Hua; Zheng, Fangfei; Chen, Meng; Patel, Jyoti; Samuels, Jonathan; Pike, Virginia C; Regatte, Ravinder; Bencardino, Jenny; Rybak, Leon; Abramson, Steven; Pillinger, Michael H

Arthritis & rheumatology. 2017 Apr 28; 69(6):1213-1220

Harrold, Leslie R; Etzel, Carol J; Gibofsky, Allan; Kremer, Joel M; Pillinger, Michael H; Saag, Kenneth G; Schlesinger, Naomi; Terkeltaub, Robert; Cox, Vanessa; Greenberg, Jeffrey D

BMC musculoskeletal disorders. 2017 Mar 14; 18(1):108-108

Kissin, Eugene Y; Pillinger, Michael H

Arthritis & rheumatology. 2017 Feb; 69(2):249-252

Igel, Talia F; Krasnokutsky, Svetlana; Pillinger, Michael H

F1000Research. 2017; 6:247-247

Teperman, Jacob; Carruthers, David; Guo, Yu; Barnett, Mallory P; Harris, Adam A; Sedlis, Steven P; Pillinger, Michael; Babaev, Anvar; Staniloae, Cezar; Attubato, Michael; Shah, Binita

International journal of cardiology. 2016 Nov 14; 228:201-204