Background: Psoriasis is a chronic inflammatory skin disease that affects up to 4% of the world population, but the mechanism underlying its pathogenesis remains to be unrevealed. Herein we examined the effects of Calcitonin Gene-Related Peptide (CGRP) on an immortal human keratinocyte line HaCaT, thereby revealing the important role of CGRP in the pathogenesis of psoriasis.
Material and Methods: Upon CGRP stimulation the chemotactic capacity of HaCaT cells was evaluated in the presence of CGRP receptor antagonist and a specific p38-MAPK pathway inhibitor, respectively. Quantitative real-time PCR and ELISA were also conducted to examine the secretion of chemotactic cytokines ligand 27 (CCL27) by HaCaT cells. Furthermore, the phosphorylation status of p38 and ERK1/2, and IκBα level were detected by immunoblotting to assess the activity of MAPK and NF-κB pathways.
Results: CGRP increased CCL27 production and promoted HaCaT cell chemotactic ability in vitro, whereas pre-treatment with SB203580 or CGRP8-37 was able to reduce CGRP-enhanced chemotaxis of HaCaT cells and CCL27 production, with inactivation of p38-MAPK and NF-κB pathways.
Conclusion: CGRP can promote the bioactivities of HaCaT cells via a p38-dependent and NF-κBdependent pathway, whose blockage may contribute to further clinical psoriatic treatment.Author(s): Gui-lian Ye, Xiu-Zhen Ren, Li-guo Qi, Li-xiang Wang, You-can Zhang