Diverse patterns of cyclooxygenase-independent metalloproteinase gene regulation in human monocytes

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dc.contributor.authorReel B.
dc.contributor.authorSala-Newby G.B.
dc.contributor.authorHuang W.-C.
dc.contributor.authorNewby A.C.
dc.date.accessioned2019-10-26T22:05:06Z
dc.date.available2019-10-26T22:05:06Z
dc.date.issued2011
dc.departmentEge Üniversitesien_US
dc.description.abstractBACKGROUND AND PURPOSE Matrix metalloproteinase (MMP) production from monocyte/macrophages is implicated in matrix remodelling and modulation of inflammation. However, knowledge of the patterns and mechanisms of gene regulation of MMPs and their endogenous tissue inhibitors (TIMPs) is fragmentary. MMP up-regulation may be a target for cyclooxygenase (COX) and prostaglandin (PG) receptor inhibition, but the extent and mechanisms of COX-independent MMP up-regulation are unclear. EXPERIMENTAL APPROACH We studied MMP mRNA expression and selected protein levels in human peripheral blood monocytes before and after adhesion, upon stimulation with bacterial lipopolysaccharide (LPS), PGE 2 or forskolin and after culturing with monocyte colony-stimulating factor on plastic or human fibronectin for up to 7 days. KEY RESULTS Monocyte adherence for 2 h transiently up-regulated COX-2, MMP-1, MMP-7 and MMP-10 mRNAs, and persistently up-regulated MMP-2, MMP-9, MMP-14 and MMP-19 mRNAs. LPS, PGE 2 or forskolin selectively increased MMP-1, MMP-9, MMP-10, MMP-12 and MMP-14 mRNAs. LPS increased PGE 2 production through COX but up-regulated MMP levels independently of COX. Differential dependence on inhibition of p42/44 and p38 mitogen-activated protein kinases, c-jun N-terminal kinase and inhibitor of ?B kinase2 paralleled the diverse patterns of MMP stimulation by LPS. Differentiation on plastic increased mRNA levels of MMP-7, MMP-9, MMP-12 and MMP-14 and TIMP-2 and TIMP-3 independently of COX; fibronectin accelerated MMP but not TIMP up-regulation. CONCLUSIONS AND IMPLICATIONS Adhesion, LPS stimulation and maturation of human monocytes lead to selective, COX-independent MMP and TIMP gene regulation, which is a potential target for selective inhibition by signalling kinase inhibitors. © 2011 The British Pharmacological Society.en_US
dc.identifier.doi10.1111/j.1476-5381.2011.01298.xen_US
dc.identifier.endpage1690en_US
dc.identifier.issn0007-1188
dc.identifier.issue8en_US
dc.identifier.pmid21371008en_US
dc.identifier.scopusqualityN/Aen_US
dc.identifier.startpage1679en_US
dc.identifier.urihttps://doi.org/10.1111/j.1476-5381.2011.01298.x
dc.identifier.urihttps://hdl.handle.net/11454/19223
dc.identifier.volume163en_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.relation.ispartofBritish Journal of Pharmacologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectcyclooxygenase inhibitorsen_US
dc.subjectinflammationen_US
dc.subjectmetalloproteinasesen_US
dc.subjectmonocytesen_US
dc.subjectprostaglandinsen_US
dc.subjectToll-like receptorsen_US
dc.titleDiverse patterns of cyclooxygenase-independent metalloproteinase gene regulation in human monocytesen_US
dc.typeArticleen_US

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