title: Differential expression of monocyte/macrophage- selective markers in human idiopathic pulmonary fibrosis.
abstract: Idiopathic interstitial pneumonias are a group of idiopathic interstitial lung diseases of which idiopathic pulmonary fibrosis (IPF) is the lesion of usual interstitial pneumonia. Although the pathogenic mechanisms remain incompletely understood, disease-specific changes in blood, a readily accessible biospecimen, have not been fully characterized. To identify biomarkers from blood and sera, the immune status of IPF patients and control subjects without structural lung disease was quantified by measuring cell surface markers, mRNA levels, and serum proteins. Statistically significant differences in cellular and molecular markers were observed between the 2 groups. The cytokine receptor IL-17RB was significantly higher in CD14+ peripheral blood mononuclear cells (PBMCs) from IPF patients, whereas expression of the chemokine receptor CXCR4 was lower. Gene expression analyses identified 18 differentially expressed genes out of 195 selected. Of these, EMR1, CCR3, UPAR, FCGR2A, OPN, CEACAM3, CD16a, CD18, CD11b, LTF, and LCN2 were up-regulated, whereas IL-17RB, IL-10, PDGFA, CD301/Clec10a, CD25/IL-2RA, IL-23p19, and IL-15 were down-regulated in IPF. Differentially regulated genes were in the functional areas of inflammation and cell signaling. Serum levels of UPAR and OPN were higher in IPF. These observations reveal significant differences in cell and molecular markers involved in monocyte/macrophage activation and migration, and suggest a role for IL-17RB in IPF.
authors.affiliation: Schering-Plough Biopharma, Palo Alto, California 94304, USA.
authors.forename: Bela
authors.initials: B
authors.lastname: Desai
authors.forename: Jeanine
authors.initials: J
authors.lastname: Mattson
authors.forename: Harman
authors.initials: H
authors.lastname: Paintal
authors.forename: Manjari
authors.initials: M
authors.lastname: Nathan
authors.forename: Fran
authors.initials: F
authors.lastname: Shen
authors.forename: Maribel
authors.initials: M
authors.lastname: Beaumont
authors.forename: Maria-Christina
authors.initials: MC
authors.lastname: Malinao
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: James
authors.initials: J
authors.lastname: Canfield
authors.forename: Beth
authors.initials: B
authors.lastname: Basham
authors.forename: Rene
authors.initials: R
authors.lastname: de Waal Malefyt
authors.forename: Terrill
authors.initials: T
authors.lastname: McClanahan
authors.forename: Ganesh
authors.initials: G
authors.lastname: Krishna
authors.forename: Robert
authors.initials: R
authors.lastname: Fick
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D002465:Cell Movement; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000473:pathology*; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000473:pathology*; D018123:Receptors, Interleukin / Q000502:physiology; D053722:Receptors, Interleukin-17
chemical_list: D015415:Biomarkers; C408922:IL17RB protein, human; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17