The objective of this study was to investigate the role of
MAPKAP kinase 2 (MK2) and
heat shock protein (HSP) HSP60 in the pathogenesis of a new model of severe
acute pancreatitis (AP). MK2 plays a significant role in the regulation of
cytokines. It has been shown that induction and expression of several HSPs can protect against experimental
pancreatitis. Interplay between both systems seems of high interest. Mice with a homozygous deletion of the MK2 gene were used. Severe AP was induced by combined
intraperitoneal injections of
cerulein with
lipopolysaccharide (LPS). Severity of AP was assessed by
biochemical markers and histology. The serum
IL-6 and lung
myeloperoxidase (MPO) levels were determined for assessing the extent of systemic inflammatory response. Expression of HSP25, HSP60, HSP70, and HSP90 was analyzed by Western blotting. Repeated
injections of
cerulein alone or
cerulein plus LPS (Cer+LPS) resulted in local inflammatory responses in the pancreas and corresponding systemic inflammatory changes with pronounced severity in the Cer+LPS group. Compared with the C57Bl wild-type mice, the MK2-/- mice presented with significant milder
pancreatitis and attenuated responses of serum
amylase and
trypsinogen activity. Furthermore, serum
IL-6 was decreased as well as lung MPO activity. Injection of LPS alone displayed neither pancreatic inflammatory responses nor alterations of pancreatic
enzyme activities but evidently elevated serum
IL-6 levels and increased lung MPO activity. In contrast hereto, in the MK2-/- mice, these changes were much milder. Increased expression of HSP25 and HSP60 occurred after induction of AP. Especially, HSP60 was robustly elevated after Cer+LPS treatment, in both MK2-/- and wild-type mice. Thus the homozygous deletion of the MK2 gene ameliorates the severity of
acute pancreatitis and accompanying systemic inflammatory reactions in a new model of severe
acute pancreatitis. Our data support the hypothesis that MK2 participates in the multifactorial regulation of early inflammatory responses in AP, independently of the regulation of
stress proteins like HSP25 and HSP60 and most likely due to its effect on
cytokine regulation.