Idiopathic pulmonary fibrosis fibroblasts migrate and proliferate to CC chemokine ligand 21.

Abstract

Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP) is the severest form of idiopathic interstitial pneumonia for which therapeutic targets are needed. Surgical lung biopsy specimens from IPF/UIP patients exhibit focal expression of CC chemokine receptor (CCR) 7, but the identity of these CCR7-positive cells is unknown. The purpose of the present study was to examine the functional and signalling significance of CCR7 expression of primary fibroblasts grown from IPF/UIP and normal surgical lung biopsy specimens. Primary fibroblasts were cultured from surgical lung biopsy specimens from IPF/UIP and normal patients. Fibroblasts treated with or without CC chemokine ligand (CCL) 21 were analysed for functional, transcriptional and proteomic differences using immunocytochemical analysis, gene arrays, Taqman real-time PCR, and migration, proliferation and Western blot assays. CCR7 was expressed by IPF/UIP fibroblasts, but not normal fibroblasts. IPF/UIP fibroblasts, but not normal fibroblasts, showed significant migratory and proliferative responses when exposed to CCL21, which were inhibited by pertussis toxin or neutralising antibodies to CCR7. Exposure of IPF/UIP fibroblasts to CCL21 altered the phosphorylation status of mitogen-activated protein kinase kinase 1/2, extracellular signal-regulated kinase 1/2 and ribosomal S6 kinase (90 kDa) in these cells; this was abrogated by pertussis toxin or CCR7-specific small interfering RNA. Together, these data demonstrate that CC chemokine ligand 21 modulates the functional properties of idiopathic pulmonary fibrosis/usual interstitial pneumonia fibroblasts, but not normal fibroblasts.

• Authors: E M Pierce, K Carpenter, C Jakubzick, S L Kunkel, H Evanoff, K R Flaherty, F J Martinez, G B Toews, C M Hogaboam
• Journal: The European respiratory journal (Eur Respir J) Vol. 29 Issue 6 Pg. 1082-93 (Jun 2007) ISSN: 0903-1936 [Print] England
• PMID: 17331965 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• CCL21 protein, human
• CCL5 protein, human
• CCR7 protein, human
• Chemokine CCL21
• Chemokine CCL5
• Chemokines, CC
• Ligands
• Receptors, CCR7
• Receptors, Chemokine

Topics

• Biopsy
• Cell Movement
• Cell Proliferation
• Chemokine CCL21
• Chemokine CCL5
• Chemokines, CC (genetics, metabolism)
• Fibroblasts (cytology, metabolism)
• Gene Expression Regulation
• Gene Silencing
• Humans
• Immunohistochemistry (methods)
• Ligands
• Lung (pathology)
• Pneumonia (metabolism)
• Pulmonary Fibrosis (metabolism, pathology)
• Receptors, CCR7
• Receptors, Chemokine (metabolism)