title: Regulation of chemokine expression by NaCl occurs independently of cystic fibrosis transmembrane conductance regulator in macrophages.
abstract: Chronic pulmonary inflammation and infection are the leading causes of morbidity and mortality in cystic fibrosis (CF). While the effect of mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) on airways remains controversial, some groups have demonstrated increases in Na(+) and Cl(-) in CF airway surface liquid compared to normal airways. We investigated the consequences of NaCl on pro-inflammatory chemokine and cytokine production by macrophages. Stimulation of mouse macrophages with increasing amounts of NaCl induced macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-alpha (TNF-alpha) production. Further, co-incubation of macrophages with NaCl in the presence of either lipopolysaccharide (LPS) or TNF-alpha synergistically increased MIP-2 production. Both the NaCl and NaCl plus LPS responses were partially dependent on endogenous production and autocrine signaling by TNF-alpha. To investigate the role of CFTR in MIP-2 production, we compared the responses of wild-type and DeltaF508 CF mouse macrophages to NaCl and LPS. The responses of macrophages from both strains were indistinguishable. In addition, CFTR mRNA was not expressed in macrophages. Taken together, these findings suggest that NaCl stimulates MIP-2 production by macrophages through a mechanism that is partially dependent on TNF-alpha but independent of macrophage CFTR expression.
authors.affiliation: Department of Immunology, University of Colorado Health Sciences Center, Denver, Colorado, USA.
authors.forename: Amanda G
authors.initials: AG
authors.lastname: Kostyk
authors.forename: Karen M
authors.initials: KM
authors.lastname: Dahl
authors.forename: Murry W
authors.initials: MW
authors.lastname: Wynes
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Whittaker
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weiss
authors.forename: Roberto
authors.initials: R
authors.lastname: Loi
authors.forename: David W H
authors.initials: DW
authors.lastname: Riches
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054426:Chemokine CXCL2; D018925:Chemokines / Q000096:biosynthesis*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012965:Sodium Chloride / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D012965:Sodium Chloride