2010
DOI: 10.1371/journal.ppat.1001192
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MAP Kinase Phosphatase-2 Plays a Critical Role in Response to Infection by Leishmania mexicana

Abstract: In this study we generated a novel dual specific phosphatase 4 (DUSP4) deletion mouse using a targeted deletion strategy in order to examine the role of MAP kinase phosphatase-2 (MKP-2) in immune responses. Lipopolysaccharide (LPS) induced a rapid, time and concentration-dependent increase in MKP-2 protein expression in bone marrow-derived macrophages from MKP-2+/+ but not from MKP-2−/− mice. LPS-induced JNK and p38 MAP kinase phosphorylation was significantly increased and prolonged in MKP-2−/− macrophages wh… Show more

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Cited by 74 publications
(115 citation statements)
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References 39 publications
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“…DUSP10 (also named MKP5) is a positive regulator in T cell proliferation and T cell-mediated immune responses (22). DUSP4 (also named MKP2) suppresses CD4 + T cell proliferation but induces normal Th1/Th2 responses following KLH immunization (23), whereas DUSP4 enhances Th1 responses following Leishmania mexicana infection (21). To our knowledge, our study demonstrates for the first time a novel immune function for DUSP14 in T cells in vivo.…”
Section: Discussionmentioning
confidence: 84%
See 1 more Smart Citation
“…DUSP10 (also named MKP5) is a positive regulator in T cell proliferation and T cell-mediated immune responses (22). DUSP4 (also named MKP2) suppresses CD4 + T cell proliferation but induces normal Th1/Th2 responses following KLH immunization (23), whereas DUSP4 enhances Th1 responses following Leishmania mexicana infection (21). To our knowledge, our study demonstrates for the first time a novel immune function for DUSP14 in T cells in vivo.…”
Section: Discussionmentioning
confidence: 84%
“…Only two DUSPs (DUSP4 and DUSP10) are reported to be involved in T cell activation and T cell-mediated immune responses using KO mice (21)(22)(23). DUSP10 (also named MKP5) is a positive regulator in T cell proliferation and T cell-mediated immune responses (22).…”
Section: Discussionmentioning
confidence: 99%
“…Heterozygote MKP-2 mice backcrossed on a C57BL/6J background generated homozygous and wild-type littermates that were used for breeding colonies (Al-Mutairi et al, 2010). All breeding and experimentation were in accordance with UK legislation [Animals (Scientific Procedures) Act 1986] and with approval by the University of Strathclyde Ethics Committee.…”
Section: Animalsmentioning
confidence: 99%
“…The MAPK and NF-κB signaling pathways are crucial mediators of proinflammatory cytokine production in macrophages (9)(10)(11)(12). To determine the mechanism underlying the anti-inflammatory activities of EPREGO in RAW264.7 cells, the MAPK pathways were investigated by detecting the phosphorylation levels of ERK, JNK and p38.…”
Section: Eprego Decreases Cellular Ros Levels and Macrophage Phagocytmentioning
confidence: 99%
“…In macrophages, the MAPK signaling pathway is one of the most extensively investigated intracellular signaling cascades involved in the LPS-induced inflammatory response (5)(6)(7)(8). The MAPK pathway is comprised of at least three signaling components: Extracellular signal-regulated kinases 1/2 (ERK 1/2); c-Jun N-terminal kinase (JNK); and p38 MAPK, all of which have been demonstrated to induce the release of immune-related cytotoxic factors and proinflammatory cytokines (9)(10)(11). Furthermore, NF-κB is important for controlling innate and adaptive immunity, and for regulating the expression of various genes during the inflammatory response (12 Activated NF-κB translocates into the nucleus of the cell and interacts with κB-binding sites in the promoter regions of target genes, in order to regulate the transcription of proinflammatory genes, including inducible nitric oxide synthase (iNOS), TNF-α and IL-6 (13,14).…”
Section: Introductionmentioning
confidence: 99%