1. ¹Center for Craniofacial Molecular Biology, University of Southern California, School of Dentistry, Los Angeles, California, USA
2. ²Division of Dermatology, Department of Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA
3. ³Department of Pathology, Kenneth Norris Jr. Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, California, USA
4. ⁴Department of Pathology, Harbor-UCLA Medical Center, Torrance, California, USA
5. ⁵Department of Oral Biology and Medicine, University of California, Los Angeles, California, USA
6. ⁶Department of Surgical, Therapeutic and Bioengineering Sciences, University of Southern California, School of Dentistry, Los Angeles, California, USA

Correspondence: Dr Anh D. Le, Department of Surgical, Therapeutic and Bioengineering Sciences, School of Dentistry, Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, California 90033, USA. E-mail: anhle@usc.edu

Received 8 March 2006; Revised 19 May 2006; Accepted 30 May 2006; Published online 13 July 2006.

Abstract

Keloid, a chronic fibro-proliferative disease, exhibits distinctive histological features characterized by an abundant extracellular matrix stroma, a local infiltration of inflammatory cells including mast cells (MCs), and a milieu of enriched cytokines. Previous studies have demonstrated that co-culture with MCs stimulate type I collagen synthesis in fibroblasts, but the signaling mechanisms remain largely unknown. In this study, we investigated the signaling pathways involved in MC-stimulated type I collagen synthesis and the effects of green tea extract (GTE) and its major catechin, (-)-epigallocatechin-3-gallate (EGCG), on collagen homeostasis in keloid fibroblasts. Our results showed that MCs significantly stimulated type I collagen expression in keloid fibroblasts, and the upregulation of type I collagen was significantly attenuated by blockade of phosphatidylinositol-3-kinase (PI-3K), mammalian target of rapamycin (mTOR), and p38 MAPK signaling pathways, but not by blockade of ERK1/2 pathway. Furthermore, GTE and EGCG dramatically inhibited type I collagen production possibly by interfering with the PI-3K/Akt/mTOR signaling pathway. Our findings suggest that interaction between MCs and keloid fibroblasts may contribute to excessive collagen accumulation in keloids and imply a therapeutic potential of green tea for the intervention and prevention of keloids and other fibrotic diseases.