New Approaches to the Treatment of Inflammatory Disorders Small Molecule inhibitors of p38 MAP Kinase

Peifer, Christian; Wagner, Gerd K.; Laufer, Stefan

doi:10.2174/156802606775270323

Cited by 130 publications

(92 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It occupies a central role in the regulation of inflammation, and its persistent activation causes the production of the inflammatory cytokines, leading to cascade of effects (Peifer et al, 2006). Following the stimulation of various pathogenic factors of ALI/ARDS, p38 MAPK can be activated.…”

Section: Discussionmentioning

confidence: 99%

“…However, the influence of p38 MAPK on inflammation associated with ALI induced by SIV subtype H9N2 (H9N2-SIV) has not been reported previously. SB203580 is one of the most commonly used p38 MAPK inhibitors, and it inhibits p38 MAPK phosphorylation without affecting ERK1/2, JNK, and ERK5 (Ono et al, 2000;Peifer et al, 2006). Previous studies suggested that through the inhibition of p38 MAPK activation and expression, SB203580 effectively inhibited the expression of inflammatory cytokines such as TNF-α and IL-1β, reduced the permeability of pulmonary capillary, and prevented pathological damage in the lungs.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Roles of p38 MAPK in the regulation of the inflammatory response to swine influenza virus-induced acute lung injury in mice

Wei¹,

Huang²,

Zhang³

et al. 2014

View full text Add to dashboard Cite

Summary. -Swine influenza virus (SIV), one of the most important zoonotic agents, is associated with major public health concerns. The current study was conducted to investigate the role of p38 mitogen-activated protein kinase (p38 MAPK) in the regulation of the inflammatory response to acute lung injury (ALI) induced by SIV of H9N2 subtype (H9N2-SIV) in mice. For this purpose, BALB/c mice were intranasally infected with 20 LD 50 of H9N2-SIV (infected group), while non-infected mice served as control (control group). To assess the effect of p38 MAPK, its specific inhibitor SB203580 was employed followed by SIV infection (SB group). At various times after infection, mouse lungs were subjected to pathological and histological observations and detection of inflammatory cytokines tumor necrosis factor α (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 and phosphorylated p38 MAPK. The obtained results showed obvious inflammatory responses, injury and raised levels of inflammatory cytokines and phosphorylated p38 MAPK in the lungs of virus-infected mice. In the mice inoculated with the virus alone, the level of phosphorylated p38 MAPK increased from day 2 and peaked at day 6 post infection (p.i.). However, SB203580 caused lower increases in inflammatory cytokines and phosphorylated p38 MAPK and a milder lung injury. These findings indicate that the activation of p38 MAPK upregulated the inflammatory responses to H9N2-SIV-induced ALI, increased its severity and promoted the production of inflammatory cytokines.Keywords: p38 MAPK; swine influenza virus; inflammatory response; acute lung injury; SB203580; mouse * Corresponding author. E-mail: hbzjkwd@163.com; xutong1969@ sohu.com; phone: +86-18931318516. Abbreviations: ALI = acute lung injury; IL = interleukin; MAPK = mitogen-activated protein kinase; p.i. = post infection; i.p. = intraperitoneally; SB group = SB203580; SIV = swine influenza virus; TNF-α = tumor necrosis factor α; W/D = wet/dry weight ratios

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Roles of p38 MAPK in the regulation of the inflammatory response to swine influenza virus-induced acute lung injury in mice

Wei¹,

Huang²,

Zhang³

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Several inhibitors of p38MAPK the prototypical pyridinyl imidazole have been characterized in vitro and some are advanced into clinical trials. However, they might block the biosynthesis of various other proinflammatory cytokines [93].…”

Section: Therapeutic Applications Of Inflammasome Inhibitorsmentioning

confidence: 99%

Strategies that modulate inflammasomes—insights from host–pathogen interactions

2007

View full text Add to dashboard Cite

/npsi/ctrl?action=rtdoc&an=8934216&lang=en http://nparc.cisti-icist.nrc-cnrc.gc.ca/npsi/ctrl?action=rtdoc&an=8934216&lang=frAccess and use of this website and the material on it are subject to the Terms and Conditions set forth at http://nparc.cisti-icist.nrc-cnrc.gc.ca/npsi/jsp/nparc_cp.jsp?lang=en NRC Publications Archive Archives des publications du CNRCThis publication could be one of several versions: author's original, accepted manuscript or the publisher's version. / La version de cette publication peut être l'une des suivantes : la version prépublication de l'auteur, la version acceptée du manuscrit ou la version de l'éditeur. For the publisher's version, please access the DOI link below./ Pour consulter la version de l'éditeur, utilisez le lien DOI ci-dessous.http://dx.doi.org/10.1007/s00281-007-0080-5Seminars in Immunopathology, 29, 3, pp. 261-274, 2007 Strategies that modulate inflammasomes-insights from host-pathogen interactions Johnston, James B; Rahman, Masmudur; McFadden, Grant Abstract The innate immune system is a dynamic and complex network for recognizing and responding to cellular insult or tissue damage after infection or injury. The primary effector mechanism of innate immunity is the generation of acute and chronic inflammatory responses through regulation of the processing and activation of proinflammatory caspases, particularly caspase 1, and cytokines, most notably IL-1β and IL-18. Inflammasomes, cytosolic multi-protein complexes that function as molecular scaffolds for caspase activation, have recently emerged as the pivotal mechanism by which host innate immune and inflammatory responses are regulated. In this review, we investigate the mechanisms by which inflammasomes are modulated, both by endogenous host systems and by microbial pathogens.

show abstract

“…It has been shown, however, that tumor necrosis factor alpha (TNFa) and other inflammatory factors can activate odontoblastic precursors and stimulate their proliferation and differentiation in response to bacterial infection [16,26,27]. Other studies have shown that the downstream targets of TNFa, the p38 mitogen-activated protein kinase (p38 MAPK) [27][28][29] and the insulin-like growth factor 1 receptor (IGF-1R) [30][31][32], also control odontoblast differentiation [33][34][35] and development [36,37]. However, studies on modulation of DPSC are limited.…”

Section: Introductionmentioning

confidence: 99%

Insulin-Like Growth Factor 1 Receptor and p38 Mitogen-Activated Protein Kinase Signals Inversely Regulate Signal Transducer and Activator of Transcription 3 Activity to Control Human Dental Pulp Stem Cell Quiescence, Propagation, and Differentiation

Vandomme

Touil

Ostyn

et al. 2014

Stem Cells and Development

View full text Add to dashboard Cite

Dental pulp stem cells (DPSCs) remain quiescent until activated in response to severe dental pulp damage. Once activated, they exit quiescence and enter regenerative odontogenesis, producing reparative dentin. The factors and signaling molecules that control the quiescence/activation and commitment to differentiation of human DPSCs are not known. In this study, we determined that the inhibition of insulin-like growth factor 1 receptor (IGF-1R) and p38 mitogen-activated protein kinase (p38 MAPK) signaling commonly activates DPSCs and promotes their exit from the G0 phase of the cell cycle as well as from the pyronin Y low stem cell compartment. The inhibition of these two pathways, however, inversely determines DPSC fate. In contrast to p38 MAPK inhibitors, IGF-1R inhibitors enhance dental pulp cell sphere-forming capacity and reduce the cells' colony-forming capacity without inducing cell death. The inverse cellular changes initiated by IGF-1R and p38 MAPK inhibitors were accompanied by inverse changes in the levels of active signal transducer and activator of transcription 3 (STAT3) factor, inactive glycogen synthase kinase 3, and matrix extracellular phosphoglycoprotein, a marker of early odontoblast differentiation. Our data suggest that there is cross talk between the IGF-1R and p38 MAPK signaling pathways in DPSCs and that the signals provided by these pathways converge at STAT3 and inversely regulate its activity to maintain quiescence or to promote self-renewal and differentiation of the cells. We propose a working model that explains the possible interactions between IGF-1R and p38 MAPK at the molecular level and describes the cellular consequences of these interactions. This model may inspire further fundamental study and stimulate research on the clinical applications of DPSC in cellular therapy and tissue regeneration.

show abstract

New Approaches to the Treatment of Inflammatory Disorders Small Molecule inhibitors of p38 MAP Kinase

Cited by 130 publications

References 70 publications

Roles of p38 MAPK in the regulation of the inflammatory response to swine influenza virus-induced acute lung injury in mice

Roles of p38 MAPK in the regulation of the inflammatory response to swine influenza virus-induced acute lung injury in mice

Strategies that modulate inflammasomes—insights from host–pathogen interactions

Insulin-Like Growth Factor 1 Receptor and p38 Mitogen-Activated Protein Kinase Signals Inversely Regulate Signal Transducer and Activator of Transcription 3 Activity to Control Human Dental Pulp Stem Cell Quiescence, Propagation, and Differentiation

Contact Info

Product

Resources

About