Fractalkine/CX3CL1 production by human airway smooth muscle cells:: induction by IFN-γ and TNF-α and regulation by TGF-β and corticosteroids

被引:77
作者
Sukkar, MB [1 ]
Issa, R [1 ]
Xie, SP [1 ]
Oltmanns, U [1 ]
Newton, R [1 ]
Chung, KF [1 ]
机构
[1] Natl Heart & Lung Inst, Imperial Coll, Dept Thorac Med, London SW3 6LY, England
关键词
chemokine; airway inflammation; asthma; chronic obstructive pulmonary disease;
D O I
10.1152/ajplung.00014.2004
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Chemokine synthesis by airway smooth muscle cells (ASMC) may be an important process underlying inflammatory cell recruitment in airway inflammatory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Fractalkine (FKN) is a recently described CX3C chemokine that has dual functions, serving as both a cell adhesion molecule and a chemoattractant for monocytes and T cells, expressing its unique receptor, CX(3)CR1. We investigated FKN expression by human ASMC in response to the proinflammatory cytokines IL-1beta, TNF-alpha, and IFN-gamma, the T helper 2-type cytokines IL-4, IL-10, and IL-13, and the fibrogenic cytokine transforming growth factor (TGF)-beta. Neither of these cytokines alone had any significant effect on ASMC FKN production. Combined stimulation with IFN-gamma and TNF-alpha induced FKN mRNA and protein expression in a time- and concentration-dependent manner. TGF-beta had a significant inhibitory effect on cytokine-induced FKN mRNA and protein expression. Dexamethasone (10(-8)-10(-6) M) significantly upregulated cytokine-induced FKN mRNA and protein expression. Finally, we used selective inhibitors of the mitogen-activated protein kinases c-Jun NH2-terminal kinase (JNK) (SP-610025), p38 (SB-203580), and extracellular signal-regulated kinase (PD-98095) to investigate their role in FKN production. SP-610025 (25 muM) and SB-203580 (20 muM), but not PD-98095, significantly attenuated cytokine-induced FKN protein synthesis. IFN-gamma- and TNF-alpha-induced JNK phosphorylation remained unaltered in the presence of TGF-beta but was inhibited by dexamethasone, indicating that JNK is not involved in TGF-beta- or dexamethasone-mediated regulation of FKN production. In summary, FKN production by human ASMC in vitro is regulated by inflammatory and anti-inflammatory factors.
引用
收藏
页码:L1230 / L1240
页数:11
相关论文
共 62 条
[1]   Tumor necrosis factor-α induces fractalkine expression preferentially in arterial endothelial cells and mithramycin A suppresses TNF-α-induced fractalkine expression [J].
Ahn, SY ;
Cho, CH ;
Park, KY ;
Lee, HJ ;
Lee, S ;
Park, SK ;
Lee, IK ;
Koh, GY .
AMERICAN JOURNAL OF PATHOLOGY, 2004, 164 (05) :1663-1672
[2]  
Amrani Y, 2001, MOL PHARMACOL, V60, P646
[3]   Fractalkine preferentially mediates arrest and migration of CD16+ monocytes [J].
Ancuta, P ;
Rao, R ;
Moses, A ;
Mehle, A ;
Shaw, SK ;
Luscinskas, FW ;
Gabuzda, D .
JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 197 (12) :1701-1707
[4]   Interleukin-9 influences chemokine release in airway smooth muscle: role of ERK [J].
Baraldo, S ;
Faffe, DS ;
Moore, PE ;
Whitehead, T ;
McKenna, M ;
Silverman, ES ;
Panettieri, RA ;
Shore, SA .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2003, 284 (06) :L1093-L1102
[5]   A new class of membrane-bound chemokine with a CX(3)C motif [J].
Bazan, JF ;
Bacon, KB ;
Hardiman, G ;
Wang, W ;
Soo, K ;
Rossi, D ;
Greaves, DR ;
Zlotnik, A ;
Schall, TJ .
NATURE, 1997, 385 (6617) :640-644
[6]   Tryptase-stimulated human airway smooth muscle cells induce cytokine synthesis and mast cell chemotaxis [J].
Berger, P ;
Girodet, PO ;
Begueret, H ;
Ousova, O ;
Perng, DW ;
Marthan, R ;
Walls, AF ;
de Lara, JMT .
FASEB JOURNAL, 2003, 17 (12) :2139-+
[7]   Fractalkine expression on human renal tubular epithelial cells: potential role in mononuclear cell adhesion [J].
Chakravorty, SJ ;
Cockwell, P ;
Girdlestone, J ;
Brooks, CJ ;
Savage, COS .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2002, 129 (01) :150-159
[8]   Fractalkine (CX3CL1) stimulated by nuclear factor κB (NF-κB)-dependent inflammatory signals induces aortic smooth muscle cell proliferation through an autocrine pathway [J].
Chandrasekar, B ;
Mummidi, S ;
Perla, RP ;
Bysani, S ;
Dulin, NO ;
Liu, F ;
Melby, PC .
BIOCHEMICAL JOURNAL, 2003, 373 :547-558
[9]   Inhibition by pentoxifylline of TNF-α-stimulated fractalkine production in vascular smooth muscle cells:: evidence for mediation by NF-κB down-regulation [J].
Chen, YM ;
Tu, CJ ;
Hung, KY ;
Wu, WD ;
Tsai, TJ ;
Hsieh, BS .
BRITISH JOURNAL OF PHARMACOLOGY, 2003, 138 (05) :950-958
[10]   Airway smooth muscle cells: contributing to and regulating airway mucosal inflammation? [J].
Chung, KF .
EUROPEAN RESPIRATORY JOURNAL, 2000, 15 (05) :961-968