Enhanced monocyte chemoattractant protein-3/CC chemokine ligand-7 in usual interstitial pneumonia.
Chemokines are increased and may exert effects on both inflammatory and remodeling events in idiopathic pulmonary pneumonia (IIP). Accordingly, we examined the concomitant expression of inflammatory CC chemotactic cytokines or chemokines and their corresponding receptors in surgical lung biopsies obtained at the time of disease diagnosis and pulmonary fibroblasts grown from these biopsies. By gene array analysis, upper and lower lobe biopsies and primary fibroblast lines from patients with usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia, and respiratory bronchiolitis-interstitial lung disease, but not patients without IIP, exhibited CCL7 gene expression. TAQMAN, immunohistochemical, and ELISA analyses confirmed that CCL7 was expressed at significantly higher levels in UIP lung biopsies compared with biopsies from patients with nonspecific interstitial pneumonia, respiratory bronchiolitis-interstitial lung disease, and from patients without IIP. Higher levels of CCL7 were present in cultures of IIP fibroblasts compared with non-IIP fibroblasts, and CCL5, a CCR5 agonist, significantly increased the synthesis of CCL7 by UIP fibroblasts. Together, these data suggest that CCL7 is highly expressed in biopsies and pulmonary fibroblast lines obtained from patients with UIP relative to patients with other IIP and patients without IIP, and that this CC chemokine may have a major role in the progression of fibrosis in this IIP patient group.
Choi
Esther S
ES
Department of Pathology, University of Michigan Medical School, Rm. 5216B, Med Sci I, 1301 Catherine Rd., Ann Arbor, MI 48109-0602, USA.
Jakubzick
Claudia
C
Carpenter
Kristin J
KJ
Kunkel
Steven L
SL
Evanoff
Holly
H
Martinez
Fernando J
FJ
Flaherty
Kevin R
KR
Toews
Galen B
GB
Colby
Thomas V
TV
Kazerooni
Ella A
EA
Gross
Barry H
BH
Travis
William D
WD
Hogaboam
Cory M
CM
D000328:Adult; D000368:Aged; D001988:Bronchiolitis / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D054410:Chemokine CCL7; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018945:Monocyte Chemoattractant Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*
C515450:CCL7 protein, human; D054410:Chemokine CCL7; D019742:Chemokines, CC; D016207:Cytokines; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D019707:Receptors, Chemokine