Regulation and function of the CXC chemokine ENA-78 in monocytes and its role in disease

Abstract

Epithelial neutrophil-activating protein 78 (ENA-78) is a member of the CXC chemokines and acts as a potent chemoattractant and activator of neutrophil function. On stimulation in vitro, ENA-78 is highly expressed in many cell types. ENA-78 protein levels are strongly elevated in synovial fluid and blood of patients with rheumatoid arthritis. By in situ hybridization and immunofluorescence staining, ENA-78 has been recognized as a major CXC chemokine expressed in epithelial cells of the intestinal mucosa of patients with Crohn's disease, ulcerative colitis, and acute appendicitis. A high expression of ENA-78 and interleukin-8 (IL-8) was also observed in the exocrine tissue of patients with chronic pancreatitis (CP). It is interesting to note that expression of IP-10, MIP-1alpha, and MCP-1 is high in healthy pancreatic tissue but low in tissue of patients with CP, suggesting a mutually exclusive expression of the ELR-CXC vs. non-ELR-CXC/CC chemokines. High-resolution studies of intracellular chemokines has revealed specific immunoreactivity for ENA-78 associated with the endoplasmic reticulum of many cell types. In contrast, GROalpha immunoreactivity was exclusively localized in the nucleus. Despite their common effects on neutrophil functions, the differential intracellular localization of ENA-78 and GROalpha suggests additional roles for these two chemokines in normal cell biology.

Cytokine profiling of prostatic fluid from cancerous prostate glands identifies cytokines associated with extent of tumor and inflammation

“…GITR is expressed by T regulatory cells (Treg) as well as activated T cells and NK cells. ENA-78 produced by monocytes, macrophages, fibroblasts, endothelial cells, and several types of epithelial cells is a member of the CXC family of chemokines, and acts as a potent chemoattractant and activator of neutrophil function as well as an angiogenic factor in cancer [20,21] In the cytokine antibody array portion of our study, HGF in prostatic fluid was the cytokine most increased in extensive disease cases, a finding that was confirmed statistically by ELISA. HGF, which can be derived from a variety of tissues, is known to be elevated in the serum of men with metastatic prostate cancer [22].…”

Dietary intervention-induced weight loss decreases macrophage content in adipose tissue of obese women

“…The lack of relation may be explained by the fact that these molecules are secreted into the circulation by various cells in different tissues. 35,36 Regarding the plasma levels of TNF-a, we did not find any changes in response to the weight reduction protocol. Similar conclusions were reached in several clinical studies with different lengths and types of diets recently reviewed by Klimcakova et al 37 Moreover, Mohamed-Ali et al 38 showed that AT is a poor contributor to circulating levels of TNF-a.…”

Replicative senescence of activated human hepatic stellate cells is accompanied by a pronounced inflammatory but less fibrogenic phenotype

“…Thus, more aspects on the interaction between HSCs and immune cells remain to be determined. For example, ENA-78 acts as a potent chemoattractant and activator of neutrophil function, 35 and eotaxin is a potent eosinophil chemoattractant. 36 Other cytokines and chemokines up-regulated at senescence are expressed and secreted by HSCs, such as IL-6 37 and IL-8.…”