Microarray analysis reveals CC Chemokine CCL-1 responsive gene expression in human HeLa Cells
Lauren Tal, Diane Huang, Niloufar Haque and Nasreen Haque
Summer Computer Simulation Conference 2007 (SCSC 2007)
San Diego, California (USA), July 15-18, 2007
Abstract
Human CC chemokine, CCL-1 is a chemotactic cytokine implicated in a variety of biological responses, namely inflammation and chemotaxis, in many cell types. We have previously shown that the CC chemokine, CCL-1 and its receptor CCR8 are expressed and causes migration of cancer cells: skin, melanoma, MDMA (breast cancer) and Kaposi’s sarcoma spindle cells. In the present study we examined the role of CCL-1 and its receptor CCR8 in the regulation of gene expression by microarray analysis and targeted siRNA inhibition in human cervical carcinoma (HeLa ) cells. We have found that HeLa cells constitutively express CCR8 and this expression of CCR8 is stimulated by CCL-1. Inorder to understand the underlying mechanisms we looked at gene expression during CCL1 and CCR8 mediated interactions. Affymetrix human microarray data analysis revealed that CCL-1 regulates genes that are involved in angiogenesis, apoptosis, oxidative stress and chemotaxis. CC chemokine CCL-2 (MCP-1) a potent regulator of monocyte/macrophage chemotaxis and invasion in various disease states is induced in response to CCL1. This stimulation of CCL-2 by CCL-1 was further validated by RT-PCR analysis. In corollary, targeted CCR8 siRNA inhibition down regulated CCL-2 expression further substantiating our findings. It is known that CCL2 protects human neuronal cells from tat-induced apoptosis and CCL1 is anti-apoptotic for thymic and leukemia cells. In the present study genes involved in oxidative stress are inhibited and those involved in protection against apoptosis are upregulated suggesting a common pathway for the two CC chemokines. Close examination of the role of CCL-1/CCR8 pathway in the regulation of CCL-2 and other angiogenic and/or apoptotic factors will provide important insights into vascular cell pathologies.