Fibroblasts as novel therapeutic targets in chronic inflammation

被引:141
作者
Flavell, S. J. [1 ]
Hou, T. Z. [1 ]
Lax, S. [1 ]
Filer, A. D. [1 ]
Salmon, M. [1 ]
Buckley, C. D. [1 ]
机构
[1] Univ Birmingham, MRC Ctr Immune Regulat, Rheumatol Res Grp, Div Immun & Infect, Birmingham B15 2TT, W Midlands, England
基金
英国医学研究理事会;
关键词
inflammation; fibroblasts; cancer; therapy;
D O I
10.1038/sj.bjp.0707487
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
A characteristic feature of many chronic inflammatory diseases is their persistence and predilection for certain sites. The molecular basis for such tissue tropism and failure of the inflammatory response to resolve has until relative recently remained obscure. Recent studies have strongly implicated fibroblasts as cells which contribute to disease persistence and which help define anatomical location. Therefore fibroblasts make an attractive therapeutic target as they help orchestrate the inflammatory infiltrate. Current anti-inflammatory therapies target immune cells in an attempt to inhibit the production of pro-inflammatory mediators. However an equally important target is the active induction of pro-resolution programmes responsible for the resolution of inflammation. Fibroblasts are likely to be an important source of these anti-inflammatory mediators. Therapeutic manipulation of fibroblasts and their biologically active products is an emerging concept in treating cancer and is likely to provide a novel method to achieve improved control of chronic inflammatory disease.
引用
收藏
页码:S241 / S246
页数:6
相关论文
共 52 条
[11]  
FASSBENDER HG, 1983, COLLAGEN REL RES, V3, P141
[12]   Invasive fibroblast-like synoviocytes in rheumatoid arthritis - Passive responders or transformed aggressors? [J].
Firestein, GS .
ARTHRITIS AND RHEUMATISM, 1996, 39 (11) :1781-1790
[13]   EVIDENCE OF FIBROBLAST HETEROGENEITY AND THE ROLE OF FIBROBLAST SUBPOPULATIONS IN FIBROSIS [J].
FRIES, KM ;
BLIEDEN, T ;
LOONEY, RJ ;
SEMPOWSKI, GD ;
SILVERA, MR ;
WILLIS, RA ;
PHIPPS, RP .
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY, 1994, 72 (03) :283-292
[14]   FIBROBLAST-LIKE CELLS FROM EMBRYONIC CHICK CORNEA, HEART, AND SKIN ARE ANTIGENICALLY DISTINCT [J].
GARRETT, DM ;
CONRAD, GW .
DEVELOPMENTAL BIOLOGY, 1979, 70 (01) :50-70
[15]   Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages [J].
Harrington, LE ;
Hatton, RD ;
Mangan, PR ;
Turner, H ;
Murphy, TL ;
Murphy, KM ;
Weaver, CT .
NATURE IMMUNOLOGY, 2005, 6 (11) :1123-1132
[16]   Evidence that fibroblasts derive from epithelium during tissue fibrosis [J].
Iwano, M ;
Plieth, D ;
Danoff, TM ;
Xue, C ;
Okada, H ;
Neilson, EG .
JOURNAL OF CLINICAL INVESTIGATION, 2002, 110 (03) :341-350
[17]   Epithelial-mesenchymal transition and its implications for fibrosis [J].
Kalluri, R ;
Neilson, EG .
JOURNAL OF CLINICAL INVESTIGATION, 2003, 112 (12) :1776-1784
[18]   Fibroblasts in cancer [J].
Kalluri, R ;
Zeisberg, M .
NATURE REVIEWS CANCER, 2006, 6 (05) :392-401
[19]   Reconstruction of functionally normal and malignant human breast tissues in mice [J].
Kuperwasser, C ;
Chavarria, T ;
Wu, M ;
Magrane, G ;
Gray, JW ;
Carey, L ;
Richardson, A ;
Weinberg, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (14) :4966-4971
[20]   Two sides of a cellular coin:: CD4+CD3- cells regulate memory responses and lymph-node organization [J].
Lane, PJL ;
Gaspal, FMC ;
Kim, MY .
NATURE REVIEWS IMMUNOLOGY, 2005, 5 (08) :655-660