| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
Departments of
* Medicine and
Pediatrics, and
Program in Cell Biology, National Jewish Medical and Research Center, Denver, CO 80206; and
Division of Pulmonary Science and Critical Care Medicine, University of Colorado School of Medicine, Denver, CO 80262
The p38 mitogen-activated protein kinase (MAPK) signaling pathway
regulates a wide range of inflammatory responses in many different
cells. Inhibition of p38 MAPK before exposing a cell to stress stimuli
has profound anti-inflammatory effects, but little is known about
the effects of p38 MAPK inhibition on ongoing inflammatory responses.
LPS-induced activation of p38 MAPK in human neutrophils was inhibited
by poststimulation exposure to a p38 MAPK inhibitor (M39). Release of
TNF-
, macrophage-inflammatory protein (MIP)-2 (MIP-1
), and
IL-8 by LPS-stimulated neutrophils was also reduced by poststimulation
p38 MAPK inhibition. In contrast, release of monocyte chemoattractant
protein-1 was found to be p38 MAPK independent. Ongoing chemotaxis
toward IL-8 was eliminated by p38 MAPK inhibition, although the rate of
nondirectional movement was not reduced. A murine model of acute
LPS-induced lung inflammation was used to study the effect of p38 MAPK
inhibition in ongoing pulmonary inflammation. Initial pulmonary cell
responses occur within 4 h of stimulation in this model, so M39
was administered 4 h or 12 h after exposure of the animals to
aerosolized LPS to avoid inhibition of cytokine release. Quantities of
TNF-, MIP-2, KC, or monocyte chemoattractant protein-1
recovered from bronchial alveolar lavage or serum were not changed.
Recruitment of neutrophils, but not other leukocytes, to the airspaces
was significantly reduced. Together, these data demonstrate the
selective reduction of LPS-induced neutrophil recruitment to the
airspaces, independent of suppression of other inflammatory responses.
These findings support the feasibility of p38 MAPK inhibition as
a selective intervention to reduce neutrophilic
inflammation.
This article has been cited by other articles:
|
|
 |
|
  M. T. Saavedra, A. D. Patterson, J. West, S. H. Randell, D. W. Riches, K. C. Malcolm, C. D. Cool, J. A. Nick, and C. A. Dinarello Abrogation of Anti-Inflammatory Transcription Factor LKLF in Neutrophil-Dominated Airways Am. J. Respir. Cell Mol. Biol., June 1, 2008; 38(6): 679 - 688. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Smoak, J. Madenspacher, S. Jeyaseelan, B. Williams, D. Dixon, K. R. Poch, J. A. Nick, G. S. Worthen, and M. B. Fessler Effects of Liver X Receptor Agonist Treatment on Pulmonary Inflammation and Host Defense J. Immunol., March 1, 2008; 180(5): 3305 - 3312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-T. Jia, W. Wei, B. Ma, Y. Xu, W.-J. Liu, Y. Wang, K.-Y. Lv, H.-T. Tang, D. Wei, and Z.-F. Xia Activation of p38 MAPK by Reactive Oxygen Species Is Essential in a Rat Model of Stress-Induced Gastric Mucosal Injury J. Immunol., December 1, 2007; 179(11): 7808 - 7819. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tsuruta, Y.-J. Park, G. P. Siegal, G. Liu, and E. Abraham Involvement of Vitronectin in Lipopolysaccaride-Induced Acute Lung Injury J. Immunol., November 15, 2007; 179(10): 7079 - 7086. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Petty, V. Sueblinvong, C. C. Lenox, C. C. Jones, G. P. Cosgrove, C. D. Cool, P. R. Rai, K. K. Brown, D. J. Weiss, M. E. Poynter, et al. Pulmonary Stromal-Derived Factor-1 Expression and Effect on Neutrophil Recruitment during Acute Lung Injury J. Immunol., June 15, 2007; 178(12): 8148 - 8157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. B. Allen, T. Leclair, M. Cloutier, J. Thompson-Figueroa, and J. H. T. Bates The response to recruitment worsens with progression of lung injury and fibrin accumulation in a mouse model of acid aspiration Am J Physiol Lung Cell Mol Physiol, June 1, 2007; 292(6): L1580 - L1589. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Jeyaseelan, S. K. Young, M. B. Fessler, Y. Liu, K. C. Malcolm, M. Yamamoto, S. Akira, and G. S. Worthen Toll/IL-1 Receptor Domain-Containing Adaptor Inducing IFN-beta (TRIF)-Mediated Signaling Contributes to Innate Immune Responses in the Lung during Escherichia coli Pneumonia J. Immunol., March 1, 2007; 178(5): 3153 - 3160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. R. Jog, V. R. Jala, R. A. Ward, M. J. Rane, B. Haribabu, and K. R. McLeish Heat Shock Protein 27 Regulates Neutrophil Chemotaxis and Exocytosis through Two Independent Mechanisms J. Immunol., February 15, 2007; 178(4): 2421 - 2428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ipaktchi, A. Mattar, A. D. Niederbichler, L. M. Hoesel, S. Vollmannshauser, M. R. Hemmila, G. L. Su, D. G. Remick, S. C. Wang, and S. Arbabi Attenuating Burn Wound Inflammatory Signaling Reduces Systemic Inflammation and Acute Lung Injury J. Immunol., December 1, 2006; 177(11): 8065 - 8071. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. G. Arndt, S. K. Young, K. R. Poch, J. A. Nick, S. Falk, R. W. Schrier, and G. S. Worthen Systemic Inhibition of the Angiotensin-Converting Enzyme Limits Lipopolysaccharide-Induced Lung Neutrophil Recruitment through Both Bradykinin and Angiotensin II-Regulated Pathways J. Immunol., November 15, 2006; 177(10): 7233 - 7241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-Q. Wang, K. Bdeir, S. Yarovoi, D. B. Cines, W. Fang, and E. Abraham Involvement of the Urokinase Kringle Domain in Lipopolysaccharide-Induced Acute Lung Injury J. Immunol., October 15, 2006; 177(8): 5550 - 5557. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Basit, J. Reutershan, M. A. Morris, M. Solga, C. E. Rose Jr., and K. Ley ICAM-1 and LFA-1 play critical roles in LPS-induced neutrophil recruitment into the alveolar space Am J Physiol Lung Cell Mol Physiol, August 1, 2006; 291(2): L200 - L207. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. W. LeBlanc, J. E. Albina, and J. S. Reichner The effect of PGG-{beta}-glucan on neutrophil chemotaxis in vivo J. Leukoc. Biol., April 1, 2006; 79(4): 667 - 675. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Birrell, S. Wong, K. McCluskie, M. C. Catley, E. L. Hardaker, S. Haj-Yahia, and M. G. Belvisi Second-Generation Inhibitors Demonstrate the Involvement of p38 Mitogen-Activated Protein Kinase in Post-Transcriptional Modulation of Inflammatory Mediator Production in Human and Rodent Airways J. Pharmacol. Exp. Ther., March 1, 2006; 316(3): 1318 - 1327. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Jeyaseelan, R. Manzer, S. K. Young, M. Yamamoto, S. Akira, R. J. Mason, and G. S. Worthen Toll-IL-1 Receptor Domain-Containing Adaptor Protein Is Critical for Early Lung Immune Responses against Escherichia coli Lipopolysaccharide and Viable Escherichia coli J. Immunol., December 1, 2005; 175(11): 7484 - 7495. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Pluskota, O. I. Stenina, I. Krukovets, D. Szpak, E. J. Topol, and E. F. Plow Mechanism and effect of thrombospondin-4 polymorphisms on neutrophil function Blood, December 1, 2005; 106(12): 3970 - 3978. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. G. Arndt, S. K. Young, and G. S. Worthen Regulation of Lipopolysaccharide-Induced Lung Inflammation by Plasminogen Activator Inhibitor-1 through a JNK-Mediated Pathway J. Immunol., September 15, 2005; 175(6): 4049 - 4059. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V Raia, L Maiuri, C Ciacci, I Ricciardelli, L Vacca, S Auricchio, M Cimmino, M Cavaliere, M Nardone, A Cesaro, et al. Inhibition of p38 mitogen activated protein kinase controls airway inflammation in cystic fibrosis Thorax, September 1, 2005; 60(9): 773 - 780. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Schnyder-Candrian, V. F. J. Quesniaux, F. Di Padova, I. Maillet, N. Noulin, I. Couillin, R. Moser, F. Erard, B. B. Vargaftig, B. Ryffel, et al. Dual Effects of p38 MAPK on TNF-Dependent Bronchoconstriction and TNF-Independent Neutrophil Recruitment in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome J. Immunol., July 1, 2005; 175(1): 262 - 269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Jeyaseelan, R. Manzer, S. K. Young, M. Yamamoto, S. Akira, R. J. Mason, and G. S. Worthen Induction of CXCL5 During Inflammation in the Rodent Lung Involves Activation of Alveolar Epithelium Am. J. Respir. Cell Mol. Biol., June 1, 2005; 32(6): 531 - 539. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. G. Arndt, S. K. Young, J. G. Lieber, M. B. Fessler, J. A. Nick, and G. S. Worthen Inhibition of c-Jun N-Terminal Kinase Limits Lipopolysaccharide-induced Pulmonary Neutrophil Influx Am. J. Respir. Crit. Care Med., May 1, 2005; 171(9): 978 - 986. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Fessler, S. K. Young, S. Jeyaseelan, J. G. Lieber, P. G. Arndt, J. A. Nick, and G. S. Worthen A Role for Hydroxy-Methylglutaryl Coenzyme A Reductase in Pulmonary Inflammation and Host Defense Am. J. Respir. Crit. Care Med., March 15, 2005; 171(6): 606 - 615. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Jeyaseelan, H. W. Chu, S. K. Young, M. W. Freeman, and G. S. Worthen Distinct Roles of Pattern Recognition Receptors CD14 and Toll-Like Receptor 4 in Acute Lung Injury Infect. Immun., March 1, 2005; 73(3): 1754 - 1763. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Fuhler, G. J. Knol, A. L. Drayer, and E. Vellenga Impaired interleukin-8- and GRO{alpha}-induced phosphorylation of extracellular signal-regulated kinase result in decreased migration of neutrophils from patients with myelodysplasia J. Leukoc. Biol., February 1, 2005; 77(2): 257 - 266. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Schmeck, J. Zahlten, K. Moog, V. van Laak, S. Huber, A. C. Hocke, B. Opitz, E. Hoffmann, M. Kracht, J. Zerrahn, et al. Streptococcus pneumoniae-induced p38 MAPK-dependent Phosphorylation of RelA at the Interleukin-8 Promotor J. Biol. Chem., December 17, 2004; 279(51): 53241 - 53247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Nick, C. D. Coldren, M. W. Geraci, K. R. Poch, B. W. Fouty, J. O'Brien, M. Gruber, S. Zarini, R. C. Murphy, K. Kuhn, et al. Recombinant human activated protein C reduces human endotoxin-induced pulmonary inflammation via inhibition of neutrophil chemotaxis Blood, December 15, 2004; 104(13): 3878 - 3885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Jeyaseelan, H. W. Chu, S. K. Young, and G. S. Worthen Transcriptional Profiling of Lipopolysaccharide-Induced Acute Lung Injury Infect. Immun., December 1, 2004; 72(12): 7247 - 7256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Mizgerd, M. M. Lupa, J. Hjoberg, J. C. Vallone, H. B. Warren, J. P. Butler, and E. S. Silverman Roles for early response cytokines during Escherichia coli pneumonia revealed by mice with combined deficiencies of all signaling receptors for TNF and IL-1 Am J Physiol Lung Cell Mol Physiol, June 1, 2004; 286(6): L1302 - L1310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Strassheim, K. Asehnoune, J.-S. Park, J.-Y. Kim, Q. He, D. Richter, K. Kuhn, S. Mitra, and E. Abraham Phosphoinositide 3-Kinase and Akt Occupy Central Roles in Inflammatory Responses of Toll-Like Receptor 2-Stimulated Neutrophils J. Immunol., May 1, 2004; 172(9): 5727 - 5733. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Strassheim, K. Asehnoune, J.-S. Park, J.-Y. Kim, Q. He, D. Richter, S. Mitra, J. Arcaroli, K. Kuhn, and E. Abraham Modulation of bone marrow-derived neutrophil signaling by H2O2: disparate effects on kinases, NF-{kappa}B, and cytokine expression Am J Physiol Cell Physiol, March 1, 2004; 286(3): C683 - C692. [Abstract] [Full Text]
|
|
|
|
|
|
D. Merz, R. Liu, K. Johnson, and R. Terkeltaub IL-8/CXCL8 and Growth-Related Oncogene {alpha}/CXCL1 Induce Chondrocyte Hypertrophic Differentiation J. Immunol., October 15, 2003; 171(8): 4406 - 4415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-W. Yoon, S.-H. Goh, J.-S. Chun, E.-W. Cho, M.-K. Lee, K.-L. Kim, J.-J. Kim, C.-J. Kim, and H. Poo {alpha}-Melanocyte-stimulating Hormone Inhibits Lipopolysaccharide-induced Tumor Necrosis Factor-{alpha} Production in Leukocytes by Modulating Protein Kinase A, p38 Kinase, and Nuclear Factor {kappa}B Signaling Pathways J. Biol. Chem., August 29, 2003; 278(35): 32914 - 32920. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-Y. Yang, J. J. Arcaroli, and E. Abraham Early Alterations in Neutrophil Activation Are Associated with Outcome in Acute Lung Injury Am. J. Respir. Crit. Care Med., June 1, 2003; 167(11): 1567 - 1574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. C. Malcolm and G. S. Worthen Lipopolysaccharide Stimulates p38-dependent Induction of Antiviral Genes in Neutrophils Independently of Paracrine Factors J. Biol. Chem., April 25, 2003; 278(18): 15693 - 15701. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
