Δημοσίευση

Attenuation of the acute inflammatory response by dual specificity phosphatase 1 by inhibition of p38 MAP kinase.

ΤίτλοςAttenuation of the acute inflammatory response by dual specificity phosphatase 1 by inhibition of p38 MAP kinase.
Publication TypeJournal Article
Year of Publication2011
AuthorsKorhonen, R., Turpeinen T., Taimi V., Nieminen R., Goulas A., & Moilanen E.
JournalMol Immunol
Volume48
Issue15-16
Pagination2059-68
Date Published2011 Sep
ISSN1872-9142
Λέξεις κλειδιάAnimals, Blotting, Western, Carrageenan, Cells, Cultured, Dual Specificity Phosphatase 1, Enzyme-Linked Immunosorbent Assay, Gene Expression, Gene Expression Regulation, Inflammation, Irritants, Macrophages, Mice, Mice, Knockout, p38 Mitogen-Activated Protein Kinases, Reverse Transcriptase Polymerase Chain Reaction, RNA, Small Interfering, Signal Transduction
Abstract

Dual specificity phosphatase 1 (DUSP1) dephosphorylates and, hence, regulates the activity of MAP kinases. The present study investigated the effect of DUSP1 on inflammatory gene expression and on the development of carrageenan-induced inflammation. It was found that DUSP1 expression was increased by LPS, and the down-regulation of DUSP1 by siRNA enhanced the phosphorylation of p38 MAPK, while JNK phosphorylation was not affected in murine macrophages. LPS-induced interleukin (IL)-6, tumor-necrosis factor (TNF) and cyclooxygenase-2 (COX2) expression were enhanced in bone marrow-derived macrophages (BMMs) from DUSP1(-/-) mice as compared to those from wild-type mice. In addition, down-regulation of DUSP1 by siRNA enhanced IL-6, TNF and COX2 expression in J774 macrophages, while p38 MAPK inhibitors SB202190 and BIRB 796 inhibited the expression of those inflammatory factors. In vivo, the intensity of the carrageenan-induced paw edema reaction was increased in DUSP1(-/-) mice as compared to the wild-type animals. In conclusion, DUSP1 is an important negative regulator of the acute inflammatory response by limiting p38 MAPK, and compounds which enhance DUSP1 expression or activity may hold a promise as anti-inflammatory drugs.

DOI10.1016/j.molimm.2011.06.439
Alternate JournalMol. Immunol.
PubMed ID21764456

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