HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/6/G1298    most recent 00530.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Tietz, A. B. Articles by Schäfer, C. Search for Related Content PubMed PubMed Citation Articles by Tietz, A. B. Articles by Schäfer, C.

INFLAMMATION/IMMUNITY/MEDIATORS

Gene deletion of MK2 inhibits TNF- and IL-6 and protects against cerulein-induced pancreatitis

¹Departments of Internal Medicine II, Klinikum Grosshadern and ²Pathology, Ludwig Maximilians University, Munich; and ³Department of Biochemistry, Hannover Medical School, Hannover; and ⁴Department of Surgery, Division of Experimental Surgery, Otto-von-Guericke-University, Magdeburg, Germany

Submitted 15 November 2005 ; accepted in final form 17 January 2006

Inflammatory effects contribute to the pathogenesis of pancreatitis. Clearly, proinflammatory cytokines like TNF- and IL-6 are involved in this process and the associated systemic complications. The MAPKAPK-2 (MK2) signaling pathway is involved in cytokine gene expression. Therefore, we hypothesized that blockade of this pathway inhibits the expression of proinflammatory cytokines and thereby protects against pancreatitis. To investigate this, we used an in vivo mouse model with a homozygous deletion of the MK2 gene. Pancreatitis was induced by injection of cerulein. The severity was determined by measuring serum lipase, pancreatic trypsin activation, pancreatic edema, and morphological changes by quantitative scoring of histological sections. Systemic inflammation was evaluated by measuring myeloperoxidase activity in lung tissue. Serum levels of TNF- and IL-6 were measured using an ELISA, and mRNA levels were identified using RT-PCR and subsequent quantitative PCR analysis. Pancreatitis in animals with deletion of the MK2 gene is less severe and accompanied with reduced serum levels of TNF- and IL-6. Pancreatic mRNA levels revealed a fourfold reduction of IL-6 mRNA expression in MK2 –/– mice. Effects were associated with suppression of pancreatic trypsin activity and reduced acinar cell injury. In summary, these data show that gene deletion of MK2 ameliorates cerulein-induced pancreatitis. TNF- and IL-6 signaling is mediated by the MK2 pathway and therefore crucial for the regulatory inflammatory processes. TNF- expression is supposably regulated by a posttranscriptional mechanism, whereas IL-6 expression is most likely regulated by transcriptional effects.

cytokines; MAPKAP kinase; actin cytoskeleton; inflammation

This article has been cited by other articles:

				Y.-Y. Li, S. Ochs, Z.-R. Gao, A. Malo, C.-J. Chen, S. Lv, E. Gallmeier, B. Goke, and C. Schafer Regulation of HSP60 and the role of MK2 in a new model of severe experimental pancreatitis Am J Physiol Gastrointest Liver Physiol, November 1, 2009; 297(5): G981 - G989. [Abstract] [Full Text] [PDF]