CD38-cyclic ADP-ribose-mediated Ca2+ signaling contributes to airway smooth muscle hyperresponsiveness

被引:137
作者
Deshpande, DA
Walseth, TF
Panettieri, RA
Kannan, MS
机构
[1] Univ Minnesota, Coll Vet Med, Dept Vet Pathobiol, St Paul, MN 55108 USA
[2] Univ Minnesota, Dept Pharmacol, St Paul, MN 55108 USA
[3] Univ Penn, Dept Med, Philadelphia, PA 19104 USA
关键词
cADPR; cytokines; inflammation;
D O I
10.1096/fj.02-0450fje
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We previously demonstrated that cyclic ADP-ribose (cADPR) elicits Ca2+ release in airway smooth muscle (ASM) cells through ryanodine receptor channels. CD38 is a cell surface protein that catalyzes the synthesis and degradation of cADPR. In inflammatory diseases such as asthma, augmented Ca2+ responses and Ca2+ sensitivity contribute to increased ASM contractility in response to agonists. In this study, we investigated the regulation of CD38 expression and the role of cADPR-mediated Ca2+ release in airway inflammation. Human ASM cells in culture between the second and fifth passages were exposed to tumor necrosis factor alpha (TNF-alpha), interleukin 1beta, or interferon gamma, or bovine serum albumin (controls). CD38 expression was measured by reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR, and Western blot analysis, and ADP-ribosyl cyclase activity was assayed with nicotinamide guanine dinucleotide as the substrate. Ca2+ responses to acetylcholine, bradykinin, and thrombin were measured in fura-2AM-loaded cells by fluorescence microscopy. Cytokines caused significant augmentation of CD38 expression, ADP-ribosyl cyclase activity, and Ca2+ responses to the agonists, compared with the control. TNF-alpha effects were greater than those of the other two cytokines. The cADPR antagonist 8-bromo-cADPR attenuated the Ca2+ responses to the agonists in control and cytokine-treated cells, with the magnitude of inhibition correlating with the level of CD38. This study provides the first demonstration of a role for CD38-cADPR signaling in a model of inflammatory airway disease.
引用
收藏
页码:452 / +
页数:25
相关论文
共 65 条
[1]   Tumor necrosis factor-α-induced secretion of RANTES and interleukin-6 from human airway smooth-muscle cells -: Modulation by cyclic adenosine monophosphate [J].
Ammit, AJ ;
Hoffman, RK ;
Amrani, Y ;
Lazaar, AL ;
Hay, DWP ;
Torphy, TJ ;
Penn, RB ;
Panettieri, RA .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2000, 23 (06) :794-802
[2]   Interferon-γ modulates cysteinyl leukotriene receptor-1 expression and function in human airway myocytes [J].
Amrani, Y ;
Moore, PE ;
Hoffman, R ;
Shore, SA ;
Panettieri, RA .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2001, 164 (11) :2098-2101
[3]  
AMRANI Y, 1993, CR ACAD SCI III-VIE, V316, P1489
[4]   Activation of tumor necrosis factor receptor 1 in airway smooth muscle: A potential pathway that modulates bronchial hyper-responsiveness in asthma? [J].
Amrani Y. ;
Chen H. ;
Panettieri Jr. R.A. .
Respiratory Research, 2000, 1 (1) :49-53
[5]  
Amrani Y, 2001, MOL PHARMACOL, V60, P646
[6]   Cytokines induce airway smooth muscle cell hyperresponsiveness to contractile agonists [J].
Amrani, Y ;
Panettieri, RA .
THORAX, 1998, 53 (08) :713-716
[7]  
Amrani Y, 1999, J IMMUNOL, V163, P2128
[8]   POTENTIATION BY TUMOR-NECROSIS-FACTOR-ALPHA OF CALCIUM SIGNALS INDUCED BY BRADYKININ AND CARBACHOL IN HUMAN TRACHEAL SMOOTH-MUSCLE CELLS [J].
AMRANI, Y ;
MARTINET, N ;
BRONNER, C .
BRITISH JOURNAL OF PHARMACOLOGY, 1995, 114 (01) :4-5
[9]   Mechanisms underlying TNF-alpha effects on agonist-mediated calcium homeostasis in human airway smooth muscle cells [J].
Amrani, Y ;
Krymskaya, V ;
Maki, C ;
Panettieri, RA .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 1997, 273 (05) :L1020-L1028
[10]   Activation of p55 tumor necrosis factor-α receptor-1 coupled to tumor necrosis factor receptor-associated factor 2 stimulates intercellular adhesion molecule-1 expression by modulating a thapsigargin-sensitive pathway in human tracheal smooth muscle cells [J].
Amrani, Y ;
Lazaar, AL ;
Hoffman, R ;
Amin, K ;
Ousmer, S ;
Panettieri, RA .
MOLECULAR PHARMACOLOGY, 2000, 58 (01) :237-245