Idiopathic pulmonary fibrosis fibroblasts migrate and proliferate to CCL21

¹ Dept of Pathology, Division of Pulmonary and Critical Care Medicine
² Dept of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI

^* To whom correspondence should be addressed. E-mail: Hogaboam{at}med.umich.edu.

	Abstract

Idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP) is the severest form of idiopathic interstitial pneumonia for which therapeutic targets are needed. Surgical lung biopsies 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 this study was to examine the functional and signaling significance of CCR7 expression of primary fibroblasts grown from IPF/UIP and normal surgical lung biopsies.

Primary fibroblasts were cultured from surgical lung biopsies from IPF/UIP and normal patients. Fibroblasts treated with or without CC chemokine ligand (CCL) 21 were analyzed for functional, transcript and proteomic differences using immunocytochemical analysis, gene arrays, Taqman real-time PCR, migration, proliferation and Western Blot assays.

CCR7 was expressed by IPF/ UIP, but not normal fibroblasts. IPF/UIP, but not normal, fibroblasts showed significant migratory and proliferative responses when exposed to CCL21, which were inhibited by pertussis toxin or neutralizing antibodies to CCR7. Exposure of IPF/UIP fibroblasts to CCL21 altered the phosphorylation status of MEK 1/2, ERK 1/2, and p90RSK in these cells, which were abrogated by pertussis toxin or CCR7-specific small interfering RNA

Together, these data demonstrate that CCL21 modulates the functional properties of IPF/UIP, but not normal fibroblasts.

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