Protein kinase Cδ mediates lysophosphatidic acid-induced NF-κB activation and interleukin-8 secretion in human bronchial epithelial cells

被引:109
作者
Cummings, R
Zhao, YT
Jacoby, D
Spannhake, EW
Ohba, M
Garcia, JGN
Watkins, T
He, DH
Saatian, B
Natarajan, V
机构
[1] Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA
[2] Oregon Hlth Sci Univ, Dept Med, Portland, OR 97239 USA
[3] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA
[4] Showa Univ, Inst Mol Oncol, Tokyo 1428555, Japan
关键词
D O I
10.1074/jbc.M404045200
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
Lysophosphatidic acid (LPA), a potent bioactive lipid, elicits many of its biological actions via the specific G-protein-coupled receptors LPA(1), LPA(2), LPA(3), and LPA(4). Recently, we have shown that LPA-induced trans-activation of platelet-derived growth factor receptor-beta is regulated by phospholipase D-2 in human bronchial epithelial cells (HBEpCs) (Wang, L., Cummings, R. J., Zhao, Y., Kazlauskas, A., Sham, J., Morris, A., Brindley, D. N., Georas, S., and Natarajan, V. ( 2003) J. Biol. Chem. 278, 39931-39940). Here, we report that protein kinase Cdelta (PKCdelta) mediates LPA-induced NF-kappaB transcription and interleukin-8 (IL-8) secretion in HBEpCs. Treatment of HBEpCs with LPA increased both IL-8 gene and protein expression, which was coupled to G(i) and G(12/13) proteins. LPA caused a marked activation of NF-kappaB in HBEpCs as determined by IkappaB phosphorylation and of NF-kappaB nuclear translocation and a strong induction of NF-kappaB promoter-mediated luciferase activity. Furthermore, LPA-activated PKCdelta and the LPA-mediated activation of NF-kappaB and IL-8 production were attenuated by overexpression of dominant-negative PKCdelta and rottlerin. Intratracheal administration of LPA in mice resulted in elevated levels of macrophage inflammatory protein-2, a murine homolog of IL-8, and an influx of neutrophils in the bronchoalveolar lavage fluid. These results demonstrate for the first time that LPA is a potent stimulator of IL-8 production in HBEpCs, which involves PKCdelta/NF-kappaB signaling pathways.
引用
收藏
页码:41085 / 41094
页数:10
相关论文
共 44 条
[11]   Dual effects of lysophosphatidic acid on human airway smooth muscle cell proliferation and survival [J].
Ediger, TL ;
Toews, ML .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2001, 1531 (1-2) :59-67
[12]   Mechanisms for lysophosphatidic acid-induced cytokine production in ovarian cancer cells [J].
Fang, XJ ;
Yu, SX ;
Bast, RC ;
Liu, SY ;
Xu, HJ ;
Hu, SX ;
LaPushin, R ;
Claret, FX ;
Aggarwal, BB ;
Lu, YL ;
Mills, GB .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (10) :9653-9661
[13]   Production of interleukin-8, RANTES and MCP-1 in intrinsic and extrinsic asthmatics [J].
Folkard, SG ;
Westwick, J ;
Millar, AB .
EUROPEAN RESPIRATORY JOURNAL, 1997, 10 (09) :2097-2104
[14]   Adenoviral E1A primes alveolar epithelial cells to PM10-induced transcription of interleukin-8 [J].
Gilmour, PS ;
Rahman, I ;
Hayashi, S ;
Hogg, JC ;
Donaldson, K ;
MacNee, W .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2001, 281 (03) :L598-L606
[15]   Gelsolin finding and cellular presentation of lysophosphatidic acid [J].
Goetzl, EJ ;
Lee, H ;
Azuma, T ;
Stossel, TP ;
Turck, CW ;
Karliner, JS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (19) :14573-14578
[16]   Inflammatory cytokines in patients with persistence of the acute respiratory distress syndrome [J].
Goodman, RB ;
Strieter, RM ;
Martin, DP ;
Steinberg, KP ;
Milberg, JA ;
Maunder, RJ ;
Kunkel, SL ;
Walz, A ;
Hudson, LD ;
Martin, TR .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1996, 154 (03) :602-611
[17]   Lysophospholipids and their G protein-coupled receptors in inflammation and immunity [J].
Gräler, MH ;
Goetzl, EJ .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2002, 1582 (1-3) :168-174
[18]   Lysophosphatidic acid enhances in vivo infiltration and activation of guinea pig eosinophils and neutrophils via a Rho/Rho-associated protein kinase-mediated pathway [J].
Hashimoto, T ;
Yamashita, M ;
Ohata, H ;
Momose, K .
JOURNAL OF PHARMACOLOGICAL SCIENCES, 2003, 91 (01) :8-14
[19]   Lysophosphatidic acid enhances airway response to acetylcholine in guinea pigs [J].
Hashimoto, T ;
Nakano, Y ;
Ohata, H ;
Momose, K .
LIFE SCIENCES, 2001, 70 (02) :199-205
[20]   Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma [J].
Keatings, VM ;
Collins, PD ;
Scott, DM ;
Barnes, PJ .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1996, 153 (02) :530-534