Cyclooxygenase-2 inhibitors decrease interleukin-1β-stimulated prostaglandin E2 and Il-6 production by human gingival fibroblasts

David Tipton, Jon C. Flynn, Sidney Stein, Mustafa Kh Dabbous

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Background: Previous work showed that normal and aggressive periodontitis (AgP) gingival fibroblasts produce the bone-resorbing cytokine IL-6. PGE2 is important in regulating IL-6 production. Non-steroidal anti-inflammatory drugs inhibit PG synthesis via COX-1 and/or COX-2 isoenzymes and may inhibit periodontal destruction. COX-2 is induced after cellular activation (i.e., by inflammatory cytokines such as IL-1β). Little is known about IL-1β-stimulated AgP fibroblast IL-6 and PGE2 production and their regulation by COX inhibitors. The objective of this study was to determine the effects of COX-2 inhibitors on amounts of PGE2 and IL-6 made by IL-1β-stimulated gingival fibroblasts. Methods: Gingival fibroblasts (2.5 × 104) from healthy or severe periodontitis patients were cultured in serum-free medium, with or without IL-1β (10-11M) for 24 hours, with or without the COX-1/2 inhibitor indomethacin or the selective COX-2 inhibitors NS-398, celecoxib, or rofecoxib. PGE2 and IL-6 in culture supernatants were determined by specific enzyme-linked immunosorbent assay (ELISA)s. Results: All of the COX inhibitors caused dose-dependent decreases in IL-1β-stimulated PGE2, to a maximum of >90% in all cell lines (P≤0.0001). The selective COX-2 inhibitors, but not indomethacin, caused partial (generally up to approximately 60%), dose-dependent decreases in IL-1β-stimulated IL-6 in all cell lines (P≤0.003). When exogenous PGE2 was added concurrently with COX-2 inhibitors before addition of IL-1β, IL-6 production returned to levels at or approaching that produced by cells exposed only to IL-1β (P≤0.04). Conclusion: The results suggest that COX-2 inhibition may be useful in helping to control fibroblast production of IL-6 in patients with severe periodontitis.

Original languageEnglish (US)
Pages (from-to)1754-1763
Number of pages10
JournalJournal of periodontology
Volume74
Issue number12
DOIs
StatePublished - Dec 1 2003

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Cyclooxygenase 2 Inhibitors
Interleukin-1
Dinoprostone
Interleukin-6
Fibroblasts
Aggressive Periodontitis
Periodontitis
Celecoxib
Indomethacin
Cytokines
Cell Line
Serum-Free Culture Media
Interleukin-10
Isoenzymes
Anti-Inflammatory Agents
Enzyme-Linked Immunosorbent Assay
Bone and Bones
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Periodontics

Cite this

Cyclooxygenase-2 inhibitors decrease interleukin-1β-stimulated prostaglandin E2 and Il-6 production by human gingival fibroblasts. / Tipton, David; Flynn, Jon C.; Stein, Sidney; Dabbous, Mustafa Kh.

In: Journal of periodontology, Vol. 74, No. 12, 01.12.2003, p. 1754-1763.

Research output: Contribution to journalArticle

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title = "Cyclooxygenase-2 inhibitors decrease interleukin-1β-stimulated prostaglandin E2 and Il-6 production by human gingival fibroblasts",
abstract = "Background: Previous work showed that normal and aggressive periodontitis (AgP) gingival fibroblasts produce the bone-resorbing cytokine IL-6. PGE2 is important in regulating IL-6 production. Non-steroidal anti-inflammatory drugs inhibit PG synthesis via COX-1 and/or COX-2 isoenzymes and may inhibit periodontal destruction. COX-2 is induced after cellular activation (i.e., by inflammatory cytokines such as IL-1β). Little is known about IL-1β-stimulated AgP fibroblast IL-6 and PGE2 production and their regulation by COX inhibitors. The objective of this study was to determine the effects of COX-2 inhibitors on amounts of PGE2 and IL-6 made by IL-1β-stimulated gingival fibroblasts. Methods: Gingival fibroblasts (2.5 × 104) from healthy or severe periodontitis patients were cultured in serum-free medium, with or without IL-1β (10-11M) for 24 hours, with or without the COX-1/2 inhibitor indomethacin or the selective COX-2 inhibitors NS-398, celecoxib, or rofecoxib. PGE2 and IL-6 in culture supernatants were determined by specific enzyme-linked immunosorbent assay (ELISA)s. Results: All of the COX inhibitors caused dose-dependent decreases in IL-1β-stimulated PGE2, to a maximum of >90{\%} in all cell lines (P≤0.0001). The selective COX-2 inhibitors, but not indomethacin, caused partial (generally up to approximately 60{\%}), dose-dependent decreases in IL-1β-stimulated IL-6 in all cell lines (P≤0.003). When exogenous PGE2 was added concurrently with COX-2 inhibitors before addition of IL-1β, IL-6 production returned to levels at or approaching that produced by cells exposed only to IL-1β (P≤0.04). Conclusion: The results suggest that COX-2 inhibition may be useful in helping to control fibroblast production of IL-6 in patients with severe periodontitis.",
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T1 - Cyclooxygenase-2 inhibitors decrease interleukin-1β-stimulated prostaglandin E2 and Il-6 production by human gingival fibroblasts

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AU - Dabbous, Mustafa Kh

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N2 - Background: Previous work showed that normal and aggressive periodontitis (AgP) gingival fibroblasts produce the bone-resorbing cytokine IL-6. PGE2 is important in regulating IL-6 production. Non-steroidal anti-inflammatory drugs inhibit PG synthesis via COX-1 and/or COX-2 isoenzymes and may inhibit periodontal destruction. COX-2 is induced after cellular activation (i.e., by inflammatory cytokines such as IL-1β). Little is known about IL-1β-stimulated AgP fibroblast IL-6 and PGE2 production and their regulation by COX inhibitors. The objective of this study was to determine the effects of COX-2 inhibitors on amounts of PGE2 and IL-6 made by IL-1β-stimulated gingival fibroblasts. Methods: Gingival fibroblasts (2.5 × 104) from healthy or severe periodontitis patients were cultured in serum-free medium, with or without IL-1β (10-11M) for 24 hours, with or without the COX-1/2 inhibitor indomethacin or the selective COX-2 inhibitors NS-398, celecoxib, or rofecoxib. PGE2 and IL-6 in culture supernatants were determined by specific enzyme-linked immunosorbent assay (ELISA)s. Results: All of the COX inhibitors caused dose-dependent decreases in IL-1β-stimulated PGE2, to a maximum of >90% in all cell lines (P≤0.0001). The selective COX-2 inhibitors, but not indomethacin, caused partial (generally up to approximately 60%), dose-dependent decreases in IL-1β-stimulated IL-6 in all cell lines (P≤0.003). When exogenous PGE2 was added concurrently with COX-2 inhibitors before addition of IL-1β, IL-6 production returned to levels at or approaching that produced by cells exposed only to IL-1β (P≤0.04). Conclusion: The results suggest that COX-2 inhibition may be useful in helping to control fibroblast production of IL-6 in patients with severe periodontitis.

AB - Background: Previous work showed that normal and aggressive periodontitis (AgP) gingival fibroblasts produce the bone-resorbing cytokine IL-6. PGE2 is important in regulating IL-6 production. Non-steroidal anti-inflammatory drugs inhibit PG synthesis via COX-1 and/or COX-2 isoenzymes and may inhibit periodontal destruction. COX-2 is induced after cellular activation (i.e., by inflammatory cytokines such as IL-1β). Little is known about IL-1β-stimulated AgP fibroblast IL-6 and PGE2 production and their regulation by COX inhibitors. The objective of this study was to determine the effects of COX-2 inhibitors on amounts of PGE2 and IL-6 made by IL-1β-stimulated gingival fibroblasts. Methods: Gingival fibroblasts (2.5 × 104) from healthy or severe periodontitis patients were cultured in serum-free medium, with or without IL-1β (10-11M) for 24 hours, with or without the COX-1/2 inhibitor indomethacin or the selective COX-2 inhibitors NS-398, celecoxib, or rofecoxib. PGE2 and IL-6 in culture supernatants were determined by specific enzyme-linked immunosorbent assay (ELISA)s. Results: All of the COX inhibitors caused dose-dependent decreases in IL-1β-stimulated PGE2, to a maximum of >90% in all cell lines (P≤0.0001). The selective COX-2 inhibitors, but not indomethacin, caused partial (generally up to approximately 60%), dose-dependent decreases in IL-1β-stimulated IL-6 in all cell lines (P≤0.003). When exogenous PGE2 was added concurrently with COX-2 inhibitors before addition of IL-1β, IL-6 production returned to levels at or approaching that produced by cells exposed only to IL-1β (P≤0.04). Conclusion: The results suggest that COX-2 inhibition may be useful in helping to control fibroblast production of IL-6 in patients with severe periodontitis.

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