Heterogeneity in fibroblast proliferation and survival in idiopathic pulmonary fibrosis

David M Habiel,Cory Hogaboam

doi:10.3389/fphar.2014.00002

Abstract

Idiopathic pulmonary fibrosis (IPF) is the most common form of interstitial lung disease characterized by the persistence of activated myofibroblasts resulting in excessive deposition of extracellular matrix proteins and profound tissue remodeling. Myofibroblasts have been shown to arise from interstitial fibroblasts, epithelial to mesenchymal transition of type II alveolar epithelial cells, and the differentiation of recruited fibrocytes. There are many mechanisms that are utilized by these cells for survival, proliferation, and persistent activation including up-regulation of cytokines [i.e., Interleukin 6 (IL-6) and C-C motif chemokine ligand 21 (CCL21)], cytokine receptors [i.e., Interleukin 6 Receptor 1 (IL-6R1), Glycoprotein 130 (gp130) and C-C Chemokine Receptor type 7 (CCR7)], and innate pattern recognition receptors [(PRRs; i.e., Toll Like Receptor 9 (TLR9)]. In this review, we will discuss the role of the cytokines IL-6 and CCL21, their receptors and the PRR, TLR9, in fibroblast recruitment, activation, survival, and differentiation into myofibroblasts in IPF.

Highlights

Interstitial lung diseases (ILD) are a heterogeneous group of nonneoplastic pulmonary disorders that affect 500,000 people in US and are thought to result from inflammatory and/or aberrant repair mechanisms in the lung (King, 2005)
There are many mechanisms that are utilized by these cells for survival, proliferation, and persistent activation including up-regulation of cytokines [i.e., Interleukin 6 (IL-6) and C-C motif chemokine ligand 21 (CCL21)], cytokine receptors [i.e., Interleukin 6 Receptor 1 (IL6R1), Glycoprotein 130 and C-C Chemokine Receptor type 7 (CCR7)], and innate pattern recognition receptors [(PRRs; i.e., Toll Like Receptor 9 (TLR9)]
We will review work pertaining to the responses of Idiopathic pulmonary fibrosis (IPF) lung fibroblasts to the cytokines, CCL21 and interleukin 6 (IL6), and to the pathogen associated molecular pattern (PAMP), hypomethylated CpG DNA, and its receptor TLR9

Summary

Introduction

Interstitial lung diseases (ILD) are a heterogeneous group of nonneoplastic pulmonary disorders that affect 500,000 people in US and are thought to result from inflammatory and/or aberrant repair mechanisms in the lung (King, 2005). We will discuss the role of the cytokines IL-6 and CCL21, their receptors and the PRR, TLR9, in fibroblast recruitment, activation, survival, and differentiation into myofibroblasts in IPF.

Results

Conclusion