Medicine and Health Sciences Commons^™

Rna Sequencing Reveals A Role Of Tonebp Transcription Factor In Regulation Of Pro-Inflammatory Genes In Response To Hyperosmolarity In Healthy Nucleus Pulposus Cells: A Homeostatic Response?, Zariel I. Johnson, Irving M. Shapiro, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

Transcription factor tonicity-responsive enhancer-binding protein (TonEBP/NFAT5) is critical for osmo-adaptation and extracellular matrix homeostasis of nucleus pulposus (NP) cells in their hypertonic tissue niche. Recent studies implicate TonEBP signaling in inflammatory disease and rheumatoid arthritis pathogenesis. However, broader functions of TonEBP in the disc remain unknown. RNA sequencing was performed on NP cells with TonEBP knockdown under hypertonic conditions. 1140 TonEBP-dependent genes were identified and categorized using Ingenuity Pathway Analysis. Bioinformatic analysis showed enrichment of matrix homeostasis and cytokine/chemokine signaling pathways. C-C motif chemokine ligand 2 (CCL2), interleukin 6 (IL6), tumor necrosis factor (TNF), and nitric oxide synthase 2 (NOS2) …

The Role And Regulation Of Inhibitor Of Kappa B Kinase In The Impaired Monocyte Response., Norman James Galbraith

Electronic Theses and Dissertations

Trauma, major surgery and systemic infection can lead to a subsequent immunosuppressed state which can predispose patients to nosocomial infection and death. Approximately a sixth of patients will have impaired monocyte function, as determined by decreased HLA-DR expression or decreased TNF-α production in response to ex-vivo lipopolysaccharide (LPS) stimulation. This project aimed to develop an in-vitro model of impaired monocyte function using isolated monocytes from healthy volunteers, to study the effect of monocyte impairment on IκK signaling, and determine the role of IκK in the impaired monocyte response. These studies have provided the following results:

1. Monocytes treated with low dose …

Synovial Neuronal Changes In Knee Joint Osteoarthritis, Haq Nawaz, Masood Umer, Shahryar Noordin, Bo Christer Bertilson, Jian Li, Aisha Siddiqah Ahmed, Mahmood Ahmed

Department of Surgery

Abstract Purpose: The purpose is to study whether pain and inflammation in knee joint osteoarthritis (OA) are associated with local synovial neuronal changes. Methods: Synovial biopsies were harvested from the medial and lateral knee compartments from OA patients undergoing total joint replacement surgery. All patients had predominant pain at the medial joint compartment. Pain and knee joint function were evaluated by knee society score (KSS). Synovial inflammation was analyzed by histopathological analysis and expression of growth associated protein-43 (GAP-43), sensory (SP, CGRP) and autonomic (NPY, VIP, TH) neuropeptides was studied by single and double immunohistochemistry techniques. Results: We observed reduced …