Actions of Prostaglandins on Human Nucleus Pulposus Metabolism Inferred by Cyclooxygenase 2 Inhibition of Cytokine Activated Cells

Nam Vo; Brandon Couch; Joon Lee; Gwendolyn Sowa; James Kang; Studer Rebecca

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자료유형: 학술저널

저자정보: Nam Vo (University of Pittsburgh) Brandon Couch (University of Pittsburgh) Joon Lee (University of Pittsburgh) Gwendolyn Sowa (University of Pittsburgh) James Kang (University of Pittsburgh) Studer Rebecca (University of Pittsburgh)

저널정보: 대한척추신경외과학회 Neurospine 대한척추신경외과학회지 제17권 제1호

발행연도: 2020.1

수록면: 60 - 68 (9page)

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Objective: Low back pain is frequently treated with nonsteroidal anti-inflammatory drugs (NSAIDs), but little is known about intervertebral disc metabolism of the prostaglandins that are diminished by these drugs. Hence, this study aimed at delineating prostaglandin actions in cytokine activated disc cells by comparing the response of nucleus pulposus (NP) cells to the pro-inflammatory cytokine interleukin (IL)-1β with and without cyclooxygenase 2 (COX-2) inhibition. Methods: NP cells cultured in alginate beads were activated with IL-1β±the COX-2 inhibitor Sc-58125. Media harvested from cultured cells were analyzed for prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2α), IL-6, and matrix metalloproteinase (MMP)-3 by enzymelinked immunosorbent assay and nitric oxide by Griess Reaction. Gene expression along with proteoglycan, collagen, and total protein synthesis were also measured. Results: IL-1β increased culture media PGE2 and PGF2α, but decreased proteoglycan and collagen syntheses as well as mRNA expression of the matrix genes aggrecan, versican, collagen I, and collagen II. COX-2 inhibition partially rescued proteoglycan and collagen syntheses and collagen I mRNA, but decreased collagen II mRNA IL-1β activated NP cells. COX-2 inhibition initially enhanced and subsequently reduced IL-1β induced inducible nitric oxide synthase, without altering medium nitrite. IL-1β induction of MMP-3 mRNA was increased by COX-2 inhibition at 24 and 48 hours. Conclusion: COX-2 inhibition alters the response of NP cells to IL-1β, suggesting IL-1β action on disc cells is mediated at least in part through COX-2 and its prostaglandins. COX-2 inhibition produces minimal effects on several key catabolic mediators, with the exception of MMP-3. Blocking COX-2 might be beneficial for maintaining disc matrix since it provides an overall rescue of IL-1 induced loss of matrix protein synthesis.

#Prostaglandins #COX-2 inhibition #Intervertebral disc cells #IL-1

참고문헌 (31)

참고문헌 신청

Freemont AJ / 2009 / The cellular pathobiology of the degenerate intervertebral disc and discogenic back pain / Rheumatology 48:5~10

Vo NV / 2010 / Prostaglandin E2 and prostaglandin F2α differentially modulate matrix metabolism of human nucleus pulposus cells / J Orthop Res 28:1259~1266

Hiyama A / 2015 / Response to tumor necrosis factor-α mediated inflammation involving activation of prostaglandin E2 and Wnt signaling in nucleus pulposus cells / J Orthop Res 33:1756~1768

Le Maitre CL / 2007 / Catabolic cytokine expression in degenerate and herniated human intervertebral discs : IL-1beta and TNFalpha expression profile / Arthritis Res Ther 9:R77

Weiler C / 2005 / Expression and distribution of tumor necrosis factor alpha in human lumbar intervertebral discs: a study in surgical specimen and autopsy controls / Spine 30:44~53

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