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Signal transduction pathways involving p38 MAPK, JNK, NFkB and AP-1 influences the response of chondrocytes cultured in agarose constructs to IL-1b and dynamic compression

Signal transduction pathways involving p38 MAPK, JNK, NFkB and AP-1 influences the response of chondrocytes cultured in agarose constructs to IL-1b and dynamic compression
Signal transduction pathways involving p38 MAPK, JNK, NFkB and AP-1 influences the response of chondrocytes cultured in agarose constructs to IL-1b and dynamic compression
Objective and Design: to examine whether inhibitors of the MAPK pathways will influence the response of bovine chondrocytes cultured in agarose constructs to IL-1? and dynamic compression.

Methods: dose-response studies were conducted under IL-1? conditions with either SB203580, SP600125, PDTC or curcumin. In separate experiments, constructs were treated with IL-1? and an appropriate concentration of inhibitor and subjected to 15% dynamic compression. Nitrite and PGE2 release, 35SO4 and [3H]-thymidine incorporation were subsequently measured using biochemical assays.

Results: all inhibitors reduced the IL-1? induced nitrite and PGE2 release in a dose-dependent manner. The inhibition of [3H]-thymidine incorporation by IL-1? was partially reversed with SB203580, SP600125 or curcumin, but not PDTC. In most cases, the inhibitors reduced 35SO4 incorporation with IL-1?. For the mechanical loading studies, the inhibitors reduced the compression-induced inhibition of nitrite and PGE2 release and restored [3H]-thymidine and 35SO4 incorporation.

Conclusions: the MAPK, AP-1 and NF-?B signalling pathways are involved in the upregulation of NO and PGE2 release by IL-1?. Dynamic compression stimulates cell proliferation and proteoglycan synthesis in the presence of IL-1? and/or inhibitors of the MAPKs and NF?B and AP-1 signalling pathways. This experimental approach could provide valuable information for the biophysical/pharmacological treatment of OA
1023-3830
306-313
Chowdhury, T.T.
3969bc1d-acec-4cad-b523-c8b4885fcb0a
Salter, D.
6168c00c-3eae-4f1f-bd48-af5e79e64472
Bader, D.L.
9884d4f6-2607-4d48-bf0c-62bdcc0d1dbf
Lee, D.A.
fbbf7169-d08b-4deb-ae87-a2cbd97c58e7
Chowdhury, T.T.
3969bc1d-acec-4cad-b523-c8b4885fcb0a
Salter, D.
6168c00c-3eae-4f1f-bd48-af5e79e64472
Bader, D.L.
9884d4f6-2607-4d48-bf0c-62bdcc0d1dbf
Lee, D.A.
fbbf7169-d08b-4deb-ae87-a2cbd97c58e7

Chowdhury, T.T., Salter, D., Bader, D.L. and Lee, D.A. (2008) Signal transduction pathways involving p38 MAPK, JNK, NFkB and AP-1 influences the response of chondrocytes cultured in agarose constructs to IL-1b and dynamic compression. Inflammation Research, 57 (7), 306-313. (doi:10.1007/s00011-007-7126-y).

Record type: Article

Abstract

Objective and Design: to examine whether inhibitors of the MAPK pathways will influence the response of bovine chondrocytes cultured in agarose constructs to IL-1? and dynamic compression.

Methods: dose-response studies were conducted under IL-1? conditions with either SB203580, SP600125, PDTC or curcumin. In separate experiments, constructs were treated with IL-1? and an appropriate concentration of inhibitor and subjected to 15% dynamic compression. Nitrite and PGE2 release, 35SO4 and [3H]-thymidine incorporation were subsequently measured using biochemical assays.

Results: all inhibitors reduced the IL-1? induced nitrite and PGE2 release in a dose-dependent manner. The inhibition of [3H]-thymidine incorporation by IL-1? was partially reversed with SB203580, SP600125 or curcumin, but not PDTC. In most cases, the inhibitors reduced 35SO4 incorporation with IL-1?. For the mechanical loading studies, the inhibitors reduced the compression-induced inhibition of nitrite and PGE2 release and restored [3H]-thymidine and 35SO4 incorporation.

Conclusions: the MAPK, AP-1 and NF-?B signalling pathways are involved in the upregulation of NO and PGE2 release by IL-1?. Dynamic compression stimulates cell proliferation and proteoglycan synthesis in the presence of IL-1? and/or inhibitors of the MAPKs and NF?B and AP-1 signalling pathways. This experimental approach could provide valuable information for the biophysical/pharmacological treatment of OA

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Published date: July 2008

Identifiers

Local EPrints ID: 189301
URI: https://eprints.soton.ac.uk/id/eprint/189301
ISSN: 1023-3830
PURE UUID: b07b4767-8d5b-44ca-addd-71463dcde8f3
ORCID for D.L. Bader: ORCID iD orcid.org/0000-0002-1208-3507

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Date deposited: 02 Jun 2011 11:10
Last modified: 06 Jun 2018 12:32

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