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Departments of 2 Medicine and 1 Surgery, Veterans Affairs Greater Los Angeles Healthcare System, and the University of California Los Angeles, Los Angeles, California 90073
Cytokines produced by
pancreatic acinar cells may mediate cell death and recruitment of
inflammatory cells into pancreas in pancreatitis and other disorders.
Here, we demonstrate mRNA expression for a number of cytokines in acini
isolated from rat pancreas. Using RNA from microscopically selected
individual cells, we confirmed the acinar cell as a source for cytokine
expression. Competitive RT-PCR, Western blot analysis, and
immunocytochemistry showed large amounts of monocyte chemotactic
protein-1 and interleukin-6 compared with other cytokines. Cytokine
expression was inhibited by either inhibitors of p38 mitogen-activated
protein kinase (MAPK), SB-202190 and SB-203580, or (less strongly) by
the transcription factor nuclear factor (NF)-
B inhibitor MG-132. A
combination of SB-203580 and MG-132 inhibited mRNA expression of all
cytokines by >90%. The results suggest a major role for p38 MAPK and
involvement of NF-B in cytokine expression in pancreatic acinar
cells. In contrast to isolated acini, we detected no or very low
cytokine expression in normal rat pancreas. Our results indicate that
activation of p38 MAPK, transcription factors, and cytokines occurs
during removal of the pancreas from the animal and isolation of acini.
nuclear factor-B; chemokines; interleukin-6; monocyte
chemotactic protein-1; pancreatitis
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