CCR3 chemokine expression is increased by tumor necrosis factor‐alpha in neuroblastoma cells

Abstract

Eosinophils cluster around parasympathetic nerves in asthmatic lungs and in antigen challenged animals where they mediate airway hyperreactivity. CCR3 receptors are found on eosinophils and blocking them with antagonists prevents airway hyperreactivity in antigen challenged guinea pigs. To determine what CCR3 chemokines are made by nerves during an inflammatory response, we treated human neuroblastoma cells (SK‐N‐SH) with a cytokine that is increased in asthma, tumor necrosis factor‐alpha (TNFγ; 3 to 3000 U/mL), for 24 h. We screened mRNA (by real‐time PCR) and soluble proteins (by ELISA) for known CCR3 chemokines including CCL5 (RANTES), CCL7 (MCP‐3), CCL8 (MCP‐2), CCL11 (eotaxin‐1), CCL13 (MCP‐4), CCL15 (MIP‐1d), CCL24 (eotaxin‐2), CCL26 (eotaxin‐3), and CCL28 (MEC). We found that SK‐N‐SH cells expressed mRNA for CCL5, CCL7, CCL8, and CCL11. TNFα increased mRNA expression for these same chemokines in a concentration dependent manner. TNFα also increased protein expression for three of these chemokines (CCL5, CCL7, and CCL11). Thus, neuroblastoma cells express a subset of CCR3 chemokines that can be increased by TNFα. These data suggest a mechanism whereby neurons can actively recruit eosinophils that can subsequently mediate neuronal hyperreactivity in asthma.Funded by: NIH: GM071338‐02, HL54659, HL55543, ES014601