Macrophage Deletion of p38α Partially Impairs Lipopolysaccharide-Induced Cellular Activation

Kang, Young Jun; Chen, Jianming; Otsuka, Motoyuki; Mols, Johann; Ren, Shuxun; Wang, Yinbin; Han, Jiahuai

doi:10.4049/jimmunol.180.7.5075

Cited by 141 publications

(131 citation statements)

References 68 publications

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“…The role of p38α in inflammation has also been proved in mice with tissuespecific deletion of p38α. The production of LPS-induced TNFα, IL-12, and IL-18 is significantly attenuated in macrophages lacking p38α (Kang et al, 2008). Interestingly, a recent study showed that myeloid p38α activation reduces acute inflammation by inducing anti-inflammatory gene expression in chronic skin inflammation, implicating a double-sided role of p38α in inflammation (Kim et al, 2008).…”

Section: P38 In Inflammation and Cancermentioning

confidence: 99%

MAPK signaling in inflammation-associated cancer development

2010

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Mitogen-activated protein (MAP) kinases comprise a family of protein-serine/threonine kinases, which are highly conserved in protein structures from unicellular eukaryotic organisms to multicellular organisms, including mammals. These kinases, including ERKs, JNKs and p38s, are regulated by a phosphorelay cascade, with a prototype of three protein kinases that sequentially phosphorylate one another. MAPKs transduce extracellular signals into a variety of cellular processes, such as cell proliferation, survival, death, and differentiation. Consistent with their essential cellular functions, MAPKs have been shown to play critical roles in embryonic development, adult tissue homeostasis and various pathologies. In this review, we discuss recent findings that reveal the profound impact of these pathways on chronic inflammation and, particularly, inflammation-associated cancer development.

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Section: P38 In Inflammation and Cancermentioning

confidence: 99%

MAPK signaling in inflammation-associated cancer development

2010

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“…1 and 2) suggested the possibility of MK2 being targeted by another kinase, contributing to the production of TNF-␣. Although MK2 is thought to be a downstream target of p38, some studies have reported that both p38 and ERK can activate MK2 in human neutrophils and mouse macrophages in response to inflammatory stimulation (31,32), and it remains unclear whether ERK can also activate MK2 in macrophages in response to microbial stimuli. We analyzed the activation of MK2 by measuring its phosphorylation in GPIstimulated macrophages pretreated with SB203580 and/or U0126 or PD98059 (another inhibitor of ERK activation).…”

Section: Mk2mentioning

confidence: 99%

MAPK-activated Protein Kinase 2 Differentially Regulates Plasmodium falciparum Glycosylphosphatidylinositol-induced Production of Tumor Necrosis Factor-α and Interleukin-12 in Macrophages

Zhu

Goel

et al. 2009

Journal of Biological Chemistry

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Proinflammatory responses induced by Plasmodium falciparum glycosylphosphatidylinositols (GPIs) are thought to be involved in malaria pathogenesis. In this study, we investigated the role of MAPK-activated protein kinase 2 (MK2) in the regulation of tumor necrosis factor-␣ (TNF-␣) and interleukin (IL)-12, two of the major inflammatory cytokines produced by macrophages stimulated with GPIs. We show that MK2 differentially regulates the GPI-induced production of TNF-␣ and IL-12. Although TNF-␣ production was markedly decreased, IL-12 expression was increased by 2-3-fold in GPI-stimulated MK2 ؊/؊ macrophages compared with wild type (WT) cells. MK2؊/؊ macrophages produced markedly decreased levels of TNF-␣ than WT macrophages mainly because of lower mRNA stability and translation. In the case of IL-12, mRNA was substantially higher in MK2 ؊/؊ macrophages than WT. This enhanced production is due to increased NF-B binding to the gene promoter, a markedly lower level expression of the transcriptional repressor factor c-Maf, and a decreased binding of GAP-12 to the gene promoter in MK2 ؊/؊ macrophages. Thus, our data demonstrate for the first time the role of MK2 in the transcriptional regulation of IL-12. Using the protein kinase inhibitors SB203580 and U0126, we also show that the ERK and p38 pathways regulate TNF-␣ and IL-12 production, and that both inhibitors can reduce phosphorylation of MK2 in response to GPIs and other toll-like receptor ligands. These results may have important implications for developing therapeutics for malaria and other infectious diseases.

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“…In other experiments, we reported an elevated production of IFN-g by monocytes treated with flavonoids (44) . In this context, IFN-g could act together with p38 as an activation signal of Stat-1 (59,60) that, in turn, by binding to motifs at -5 . 2 and -5 .…”

Section: Proceedings Of the Nutrition Societymentioning

confidence: 99%

Polyphenols from red wine are potent modulators of innate and adaptive immune responsiveness

Magrone

Jirillo

2010

Proc. Nutr. Soc.

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It is well known that the consumption of dietary polyphenols leads to beneficial effects for human health as in the case of prevention and/or attenuation of cardiovascular, inflammatory, neurodegenerative and neoplastic diseases. This review summarizes the role of polyphenols from red wine in the immune function. In particular, using healthy human peripheral blood mononuclear cells, we have demonstrated the in vitro ability of Negroamaro, an Italian red wine, to induce the release of nitric oxide and both pro-inflammatory and anti-inflammatory cytokines, thus leading to the maintenance of the immmune homeostasis in the host. All these effects were abrogated by deprivation of polyphenols from red wine samples. We have also provided evidence that Negromaro polyphenols are able to activate extracellular regulated kinase and p38 kinase and switch off the NF-B pathway via an increased expression with time of the IB phosphorylated form. These mechanisms may represent key molecular events leading to inhibition of the pro-inflammatory cascade and atherogenesis. In conclusion, according to the current literature and our own data, moderate consumption of red wine seems to be protective for the host in the prevention of several diseases, even including aged-related diseases by virtue of its immunomodulating properties

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Macrophage Deletion of p38α Partially Impairs Lipopolysaccharide-Induced Cellular Activation

Cited by 141 publications

References 68 publications

MAPK signaling in inflammation-associated cancer development

MAPK signaling in inflammation-associated cancer development

MAPK-activated Protein Kinase 2 Differentially Regulates Plasmodium falciparum Glycosylphosphatidylinositol-induced Production of Tumor Necrosis Factor-α and Interleukin-12 in Macrophages

Polyphenols from red wine are potent modulators of innate and adaptive immune responsiveness

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