title: Chronic ethanol inhibits CXC chemokine ligand 10 production in human A172 astroglia and astroglial-mediated leukocyte chemotaxis.
abstract: Astroglia are the most prevalent cell type in the human central nervous system (CNS) and perform important roles in normal tissue homeostasis, during pathological events and following trauma. Astroglial-derived chemokines have important neurotrophic effects and are important to CNS immunocompetence and response to injury, in part, due to their direct role in leukocyte and microglial cell recruitment. However, while ethanol is known to induce CNS pathologies and to be peripherally immunosuppressive, ethanol effects on chemokine expression in human astroglia are essentially unknown. We have demonstrated that chemotaxis of human U937 leukocytic cells, across a 0.5 microm pore polycarbonate transmembrane insert, is induced in response to culture media collected from 10 microg/ml lipopolysaccharide (LPS) + 10 ng/ml interleukin (IL)-1beta-stimulated A172 human astroglia cells. The involvement of the chemokine CXCL10 (also known as interferon-gamma inducible protein or IP-10) in astroglial-induced chemotaxis of U937 cells has been indicated, as chemotaxis can be reduced by an anti-CXCL10 neutralizing antibody. Interestingly, chemotaxis of U937 cells, in response to astroglial-exposed media, is reduced when astroglia are chronically (9 days) exposed to 50 mM ethanol before stimulation with LPS + IL-1beta. Furthermore, we observed that LPS + IL-1beta-stimulated CXCL10 production is inhibited in human A172 astroglia exposed to chronic 50 mM ethanol. Thus, alterations in astroglial CXCL10 expression may disrupt CNS immunocompetence and play an important role in ethanol-induced CNS pathologies.
authors.affiliation: Alcohol and Brain Research Laboratory, Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430-0001, USA. randall.davis@ttuhsc.edu
authors.forename: Randall L
authors.initials: RL
authors.lastname: Davis
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Syapin
mesh_terms: D000704:Analysis of Variance; D001253:Astrocytes / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D011994:Recombinant Proteins
chemical_list: C114753:CXCL10 protein, human; D002492:Central Nervous System Depressants; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D017077:Culture Media, Conditioned; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D000431:Ethanol