Mechanisms of dexamethasone-mediated chemokine down-regulation in mild and severe acute pancreatitis

S. Yubero , L. Ramudo , M.A. Manso , I. De Dios

This study aimed to investigate the role of therapeutic dexamethaxone (Dex) treatment on the mechanisms underlying chemokine expression during mild and severe acute pancreatitis (AP) experimentally induced in rats. Regardless of the AP severity, Dex (1 mg/kg), administered 1 hour after AP, reduced the acinar cell activation of extracellular signal-regulated kinase (ERK) and c-Jun-NH-terminal kinase (JNK) but failed to reduce p38-mitogen activated protein kinas (MAPK) in severe AP. In both AP models, Dex inhibited the activation of nuclear factor-κB (NF-κB) and signal transducers and activators of transcription (STAT) factors. All of this resulted in pancreatic down-regulation of the chemokines monocyte chemoattractant protein-1 (MCP-1) and cytokine-induced neutrophil chemoattractant (CINC). Lower plasma chemokine levels as well as decreased amylasemia, hematocrit and plasma interleukin-1β (Il-1β) levels were found either in mild or severe AP treated with Dex. Pancreatic neutrophil infiltration was attenuated by Dex in mild but not in severe AP. In conclusion, by targeting MAPKs, NF-κB and STAT3 pathways, Dex treatment down-regulated the chemokine expression in different cell sources during mild and severe AP, resulting in decreased severity of the disease.

Mots clés: acute pancreatitis; chemokines; dexamethasone; MAPK; NF-κB; STAT3

S. Yubero, L. Ramudo, M.A. Manso, I. De Dios. Mechanisms of dexamethasone-mediated chemokine down-regulation in mild and severe acute pancreatitis. Biochimica et Biophysica Acta - Molecular Basis of Disease, 2009, 1792 (12), pp.1205. ⟨10.1016/j.bbadis.2009.10.001⟩. ⟨hal-00537258⟩