| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Signaling in Inflammatory Bowel Disease1
* Mucosal Immunology Group, First Department of Medicine, and
Institute of Anatomy, Kiel University Medical Center, Kiel, Germany
Inflammatory bowel diseases (IBD)—Crohn’s disease and ulcerative
colitis—are relapsing chronic inflammatory disorders which involve
genetic, immunological, and environmental factors. The regulation of
TNF-
, a key mediator in the inflammatory process in IBD, is
interconnected with mitogen-activated protein kinase pathways. The aim
of this study was to characterize the activity and expression of the
four p38 subtypes (p38–
), c-Jun N-terminal kinases (JNKs), and
the extracellular signal-regulated kinases (ERK)1/2 in the inflamed
intestinal mucosa. Western blot analysis revealed that p38, JNKs,
and ERK1/2 were significantly activated in IBD, with p38 showing the
most pronounced increase in kinase activity. Protein expression of p38
and JNK was only moderately altered in IBD patients compared with
normal controls, whereas ERK1/2 protein was significantly
down-regulated. Immunohistochemical analysis of inflamed mucosal
biopsies localized the main expression of p38 to lamina propria
macrophages and neutrophils. ELISA screening of the supernatants of
Crohn’s disease mucosal biopsy cultures showed that incubation with
the p38 inhibitor SB 203580 significantly reduced secretion of TNF-.
In vivo inhibition of TNF- by a single infusion of anti-TNF-
Ab (infliximab) resulted in a highly significant transient increase of
p38 activity during the first 48 h after infusion. A
significant infliximab-dependent p38 activation was also observed in
THP-1 myelomonocytic cells. In human monocytes, infliximab enhanced
TNF- gene expression, which could be inhibited by SB 203580. In
conclusion, p38 signaling is involved in the pathophysiology of
IBD.
This article has been cited by other articles:
|
|
 |
|
  A. Till, P. Rosenstiel, K. Brautigam, C. Sina, G. Jacobs, H.-H. Oberg, D. Seegert, T. Chakraborty, and S. Schreiber A role for membrane-bound CD147 in NOD2-mediated recognition of bacterial cytoinvasion J. Cell Sci., February 15, 2008; 121(4): 487 - 495. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Garcia-Herrera, M. C. Marca, E. Brot-Laroche, N. Guillen, S. Acin, M. A. Navarro, J. Osada, and M. J. Rodriguez-Yoldi Protein kinases, TNF-{alpha}, and proteasome contribute in the inhibition of fructose intestinal transport by sepsis in vivo Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G155 - G164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-p. Yang, X.-a. Zhu, and M. O. M. Tso Role of NF-{kappa}B and MAPKs in Light-Induced Photoreceptor Apoptosis Invest. Ophthalmol. Vis. Sci., October 1, 2007; 48(10): 4766 - 4776. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Rossol, U. Meusch, M. Pierer, S. Kaltenhauser, H. Hantzschel, S. Hauschildt, and U. Wagner Interaction between Transmembrane TNF and TNFR1/2 Mediates the Activation of Monocytes by Contact with T Cells J. Immunol., September 15, 2007; 179(6): 4239 - 4248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Rosenstiel, C. Sina, C. End, M. Renner, S. Lyer, A. Till, S. Hellmig, S. Nikolaus, U. R. Folsch, B. Helmke, et al. Regulation of DMBT1 via NOD2 and TLR4 in Intestinal Epithelial Cells Modulates Bacterial Recognition and Invasion J. Immunol., June 15, 2007; 178(12): 8203 - 8211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Qin, W. Qiu, R. K. Avramoglu, and K. Adeli Tumor Necrosis Factor-{alpha} Induces Intestinal Insulin Resistance and Stimulates the Overproduction of Intestinal Apolipoprotein B48-Containing Lipoproteins Diabetes, February 1, 2007; 56(2): 450 - 461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Rassmann, A. Henke, M. Zobawa, M. Carlsohn, H.-P. Saluz, S. Grabley, F. Lottspeich, and T. Munder Proteome alterations in human host cells infected with coxsackievirus B3 J. Gen. Virol., September 1, 2006; 87(9): 2631 - 2638. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. LUGERING, P. LEBIEDZ, S. KOCH, and T. KUCHARZIK Apoptosis as a Therapeutic Tool in IBD? Ann. N.Y. Acad. Sci., August 1, 2006; 1072: 62 - 77. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. Tietz, A. Malo, J. Diebold, A. Kotlyarov, A. Herbst, F. T. Kolligs, B. Brandt-Nedelev, W. Halangk, M. Gaestel, B. Goke, et al. Gene deletion of MK2 inhibits TNF-{alpha} and IL-6 and protects against cerulein-induced pancreatitis Am J Physiol Gastrointest Liver Physiol, June 1, 2006; 290(6): G1298 - G1306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Brand, F. Beigel, T. Olszak, K. Zitzmann, S. T. Eichhorst, J.-M. Otte, H. Diepolder, A. Marquardt, W. Jagla, A. Popp, et al. IL-22 is increased in active Crohn's disease and promotes proinflammatory gene expression and intestinal epithelial cell migration Am J Physiol Gastrointest Liver Physiol, April 1, 2006; 290(4): G827 - G838. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Rosenstiel, K. Huse, A. Till, J. Hampe, S. Hellmig, C. Sina, S. Billmann, O. von Kampen, G. H. Waetzig, M. Platzer, et al. A short isoform of NOD2/CARD15, NOD2-S, is an endogenous inhibitor of NOD2/receptor-interacting protein kinase 2-induced signaling pathways PNAS, February 28, 2006; 103(9): 3280 - 3285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Weichart, J. Gobom, S. Klopfleisch, R. Hasler, N. Gustavsson, S. Billmann, H. Lehrach, D. Seegert, S. Schreiber, and P. Rosenstiel Analysis of NOD2-mediated Proteome Response to Muramyl Dipeptide in HEK293 Cells J. Biol. Chem., January 27, 2006; 281(4): 2380 - 2389. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Kuldo, J. Westra, S. A. Asgeirsdottir, R. J. Kok, K. Oosterhuis, M. G. Rots, J. P. Schouten, P. C. Limburg, and G. Molema Differential effects of NF-{kappa}B and p38 MAPK inhibitors and combinations thereof on TNF-{alpha}- and IL-1{beta}-induced proinflammatory status of endothelial cells in vitro Am J Physiol Cell Physiol, November 1, 2005; 289(5): C1229 - C1239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Lowenberg, A. Verhaar, B. van den Blink, F. ten Kate, S. van Deventer, M. Peppelenbosch, and D. Hommes Specific Inhibition of c-Raf Activity by Semapimod Induces Clinical Remission in Severe Crohn's Disease J. Immunol., August 15, 2005; 175(4): 2293 - 2300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Hollenbach, M. Vieth, A. Roessner, M. Neumann, P. Malfertheiner, and M. Naumann Inhibition of RICK/Nuclear Factor-{kappa}B and p38 Signaling Attenuates the Inflammatory Response in a Murine Model of Crohn Disease J. Biol. Chem., April 15, 2005; 280(15): 14981 - 14988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-N. Cho, J. Y. Choi, C.-H. Kim, S. J. Baek, K. C. Chung, U. Y. Moon, K.-S. Kim, W.-J. Lee, J. S. Koo, and J.-H. Yoon Prostaglandin E2 Induces MUC8 Gene Expression via a Mechanism Involving ERK MAPK/RSK1/cAMP Response Element Binding Protein Activation in Human Airway Epithelial Cells J. Biol. Chem., February 25, 2005; 280(8): 6676 - 6681. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P Rosenstiel, J Agnholt, J Kelsen, V Medici, G H Waetzig, D Seegert, S Schreiber, A D. Sabatino, R Ciccocioppo, R Morera, et al. Differential modulation of p38 mitogen activated protein kinase and STAT3 signalling pathways by infliximab and etanercept in intestinal T cells from patients with Crohn's disease * Author's reply Gut, February 1, 2005; 54(2): 314 - 316. [Full Text] [PDF]
|
|
|
|
|
|
C. L. Galindo, A. A. Fadl, J. Sha, C. Gutierrez Jr., V. L. Popov, I. Boldogh, B. B. Aggarwal, and A. K. Chopra Aeromonas hydrophila Cytotoxic Enterotoxin Activates Mitogen-activated Protein Kinases and Induces Apoptosis in Murine Macrophages and Human Intestinal Epithelial Cells J. Biol. Chem., September 3, 2004; 279(36): 37597 - 37612. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Marceau, L. Dubuquoy, C. Caucheteux-Rousseaux, B. Foligne, P. Desreumaux, and M. Simonet Yersinia pseudotuberculosis Anti-Inflammatory Components Reduce Trinitrobenzene Sulfonic Acid-Induced Colitis in the Mouse Infect. Immun., April 1, 2004; 72(4): 2438 - 2441. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Stambe, D. J. Nikolic-Paterson, P. A. Hill, J. Dowling, and R. C. Atkins p38 Mitogen-Activated Protein Kinase Activation and Cell Localization in Human Glomerulonephritis: Correlation with Renal Injury J. Am. Soc. Nephrol., February 1, 2004; 15(2): 326 - 336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kirchner, S. Boldt, W. Kolch, S. Haffner, S. Kazak, P. Janosch, E. Holler, R. Andreesen, and G. Eissner LPS resistance in monocytic cells caused by reverse signaling through transmembrane TNF (mTNF) is mediated by the MAPK/ERK pathway J. Leukoc. Biol., February 1, 2004; 75(2): 324 - 331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. S. Song, J.-K. Seong, K. C. Chung, W.-J. Lee, C.-H. Kim, K. N. Cho, C.-D. Kang, J. S. Koo, and J.-H. Yoon Induction of MUC8 Gene Expression by Interleukin-1{beta} Is Mediated by a Sequential ERK MAPK/RSK1/CREB Cascade Pathway in Human Airway Epithelial Cells J. Biol. Chem., September 12, 2003; 278(37): 34890 - 34896. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Salh, K. Assi, V. Templeman, K. Parhar, D. Owen, A. Gomez-Munoz, and K. Jacobson Curcumin attenuates DNB-induced murine colitis Am J Physiol Gastrointest Liver Physiol, June 9, 2003; 285(1): G235 - G243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D W Hommes, M P Peppelenbosch, and S J H van Deventer Mitogen activated protein (MAP) kinase signal transduction pathways and novel anti-inflammatory targets Gut, January 1, 2003; 52(1): 144 - 151. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
