Interleukin-1beta induces beta-calcitonin gene-related peptide secretion in human type II alveolar epithelial cells

Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide mainly present in sensory nerve fibers, which is present in almost all organs, but it is also found in cultured rat type II alveolar epithelial cells (AEII). Our data have previously shown that CGRP may play an important role in inflammation as an immunomodulator. Proinflammatory factor IL-1beta induces CGRP release from neuron-derived sources. However, whether IL-1beta can induce CGRP secretion from a nonneural source, AEII cells, is not known. In the present study, we demonstrated that human AEII A549 cells expressed beta-CGRP, and IL-1beta (0.001-50 ng/ml) directly increased CGRP secretion from these cells in a time- and concentration-dependent manner. The mRNA level of beta-CGRP was also elevated by IL-1beta (1 ng/ml). In addition, we found that IL-1beta-induced CGRP production was mediated through the PKC-p38 mitogen-activated protein (MAP) kinase-NF-kappaB signaling pathway. Furthermore, IL-1beta-induced chemokines MCP-1 and IL-8 were partially inhibited by exogenous hCGRP (0.1-10 nM) and potentiated by hCGRP8-37 (0.1-10 nM), a CGRP1-receptor antagonist. In addition, the CGRP-inhibited chemokine effect was partially reduced by Rp-cAMP, a cAMP-PK inhibitor. These results suggest that AEII-derived CGRP may act in an autocrine/paracrine mode and play an important inhibitory role in the local area in lung inflammatory diseases.