Anti-inflammatory effects of naproxen sodium on human osteoarthritis synovial fluid immune cells

Abstract

Objective: To evaluate the anti-inflammatory effects of clinically relevant naproxen sodium (Nx) concentrations on human monocyte-derived macrophages in a controlled in vitro system and human primary synovial fluid (SF) cells. Design: Using phorbol 12-myristate 13-acetate, THP-1 human monocytic cells were differentiated into mature monocyte-derived macrophages in vitro then treated with Nx pre-or post-activating an inflammatory response with lipopolysaccharide (LPS) and hyaluronan (HA) fragments (n ¼ 8/group). Cell culture supernatants were assessed for NF-kB activity and prostaglandin E 2 (PGE 2 ), indicating cyclooxygenase enzyme activity. Under Duke IRB approval, primary human SF cells were collected at the time of knee joint replacement (n ¼ 19 individuals) for osteoarthritis (OA), and cultured with LPS, HA and Nx; SF cells were characterized by polychromatic flow cytometry for cell surface markers and intracellular cytokines. Result: Compared to placebo treatment of THP-1 cells, low dose Nx (corresponding 27.5e440 mg/L orally) added both pre-and post-activation with LPS/HA, significantly reduced NF-kB activity and PGE2: mean reduction to 73%, 61%, 17% and 10% of placebo, respectively. LPS/HA treatment of primary OA SF cells significantly increased the number of IL-1b producing primary monocytes and macrophages, and by 24 h the overall production of secreted cytokines (IL-1b, IL-6, IL8, and TNF-a). Low dose Nx reduced the percentage of IL-1b producing primary monocytes and macrophages. Conclusion: LPS/HA induced inflammation of THP-1 monocytic and primary human SF cells. Low dose Nx both prevented and reduced inflammatory responses of a human monocytic cell line and reduced IL-1b production by primary human SF monocytes and macrophages.

Molecular profiling of individual FDA-approved clinical drugs identifies modulators of nonsense-mediated mRNA decay

“… 59 , 60 , 61 We also listed the top 15 ranked drugs that decreased the N_Ptbp2 / F_Ptbp2 , N_Hnrnpl / F_Hnrnpl , and N_Tra2b / F_Tra2b ratio ( Figures 4 D–4F). Annotations of these drugs from PubChem indicate a wide range of actions from cellular enzyme inhibitors (bestatin, naproxen sodium, pyridostigmine bromide, and pravastatin sodium), 62 , 63 , 64 , 65 inflammatory response regulators (triamcinolone acetonide, naproxen sodium, cortisone acetate, and diflunisal), 66 , 67 , 68 , 69 to antibiotic reagents (sulfacetamide, cefixime trihydrate, mafenide acetate, and ampicillin sodium). 70 , 71 , 72 , 73

Figure 4 Top 15 ranked drugs based on the NMD/non-NMD ratios of each reporter gene (A–C) Top 15 ranked drugs with possible NMD inhibition activity.

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Innate/Inflammatory Bioregulation of Surfactant Protein D Alleviates Rat Osteoarthritis by Inhibiting Toll-Like Receptor 4 Signaling

“…To validate the anti-inflammatory effect of SP-D, we stimulated the chondrocytes with LPS and analyzed LPS-stimulated inflammatory responses. Among inflammatory cytokines, the interleukin family, particularly IL-1β and TNF-α, play a leading role in the pathological progression of OA ( 28 , 29 ). During the pathological process of OA, inflammatory mediators, especially IL-1β, induce the release of other pro-inflammatory cytokines, thereby promoting the catabolic response and destroying the structure of the articular cartilage in chondrocytes.…”

Synovial Fluid in Knee Osteoarthritis Extends Proinflammatory Niche for Macrophage Polarization

“…The present work is a continuation of these published studies to investigate whether the induced inflammation can further stimulate macrophage polarization, which is primarily responsible for the inflammation in OA joints. For this, an in vitro cell differentiation assay was designed, wherein U937 and PBMC-derived CD14+ cells were treated as macrophage precursors and incubated with OA SFs of different disease severity for 48 h. The assay design was based on the knowledge that macrophage polarization in in vitro conditions can be achieved by exposing the cells to different inducing agents, like interferon-γ (IFN-γ), lipopolysaccharide (LPS), PMA, IL-1β, and TNF-α to develop proinflammatory macrophages [ 33 , 34 , 35 , 36 , 37 , 38 ]. To our knowledge this is the first report wherein the pathobiological protein milieu of the diseased SF was used as a macrophage-polarization-inducing agent.…”